[go: up one dir, main page]
Skip to main content

Advertisement

SpringerLink
Log in

RNA metabolism and links to inflammatory regulation and disease

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Inflammation is vital to protect the host against foreign organism invasion and cellular damage. It requires tight and concise gene expression for regulation of pro- and anti-inflammatory gene expression in immune cells. Dysregulated immune responses caused by gene mutations and errors in post-transcriptional regulation can lead to chronic inflammatory diseases and cancer. The mechanisms underlying post-transcriptional gene expression regulation include mRNA splicing, mRNA export, mRNA localisation, mRNA stability, RNA/protein interaction, and post-translational events such as protein stability and modification. The majority of studies to date have focused on transcriptional control pathways. However, post-transcriptional regulation of mRNA in eukaryotes is equally important and related information is lacking. In this review, we will focus on the mechanisms involved in the pre-mRNA splicing events, mRNA surveillance, RNA degradation pathways, disorders or symptoms caused by mutations or errors in post-transcriptional regulation during innate immunity especially toll-like receptor mediated pathways.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and material

Figures and tables in this manuscript were made by Hui-Chi Lai and are freely available under the Journal of Cellular and molecular life science.

References

  1. Singh RK, Cooper TA (2012) Pre-mRNA splicing in disease and therapeutics. Trends Mol Med 18(8):472–482. https://doi.org/10.1016/j.molmed.2012.06.006 (Epub 2012/07/24; PubMed PMID: 22819011; PubMed Central PMCID: PMCPMC3411911)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lopez-Bigas N, Audit B, Ouzounis C, Parra G, Guigo R (2005) Are splicing mutations the most frequent cause of hereditary disease? FEBS Lett 579(9):1900–1903. https://doi.org/10.1016/j.febslet.2005.02.047 (Epub 2005/03/29; PubMed PMID: 15792793)

    Article  CAS  PubMed  Google Scholar 

  3. Ritter SY, Subbaiah R, Bebek G, Crish J, Scanzello CR, Krastins B et al (2013) Proteomic analysis of synovial fluid from the osteoarthritic knee: comparison with transcriptome analyses of joint tissues. Arthritis Rheum 65(4):981–982. https://doi.org/10.1002/art.37823 (Epub 2013/02/13; PubMed PMID: 23400684; PubMed Central PMCID: PMCPMC3618606)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nuhrenberg TG, Langwieser N, Binder H, Kurz T, Stratz C, Kienzle RP et al (2013) Transcriptome analysis in patients with progressive coronary artery disease: identification of differential gene expression in peripheral blood. J Cardiovasc Transl Res 6(1):81–93. https://doi.org/10.1007/s12265-012-9420-5 (Epub 2012/11/29; PubMed PMID: 23188564)

    Article  PubMed  Google Scholar 

  5. Tuller T, Atar S, Ruppin E, Gurevich M, Achiron A (2013) Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases. Genes Immun 14(2):67–82. https://doi.org/10.1038/gene.2012.55 (Epub 2012/11/30; PubMed PMID: 23190644)

    Article  CAS  PubMed  Google Scholar 

  6. Kawasaki T, Kawai T (2014) Toll-like receptor signaling pathways. Front Immunol 5:461. https://doi.org/10.3389/fimmu.2014.00461 (Epub 2014/10/14; PubMed PMID: 25309543; PubMed Central PMCID: PMCPMC4174766)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Cai X, Chiu YH, Chen ZJ (2014) The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol Cell 54(2):289–296. https://doi.org/10.1016/j.molcel.2014.03.040 (Epub 2014/04/29; PubMed PMID: 24766893)

    Article  CAS  PubMed  Google Scholar 

  8. Bell JK, Mullen GE, Leifer CA, Mazzoni A, Davies DR, Segal DM (2003) Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol 24(10):528–533. https://doi.org/10.1016/s1471-4906(03)00242-4 (Epub 2003/10/14; PubMed PMID: 14552836)

    Article  CAS  PubMed  Google Scholar 

  9. O’Neill LA, Greene C (1998) Signal transduction pathways activated by the IL-1 receptor family: ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol 63(6):650–657 (Epub 1998/06/10; PubMed PMID: 9620655)

    Article  CAS  PubMed  Google Scholar 

  10. Kawai T, Akira S (2010) The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11(5):373–384. https://doi.org/10.1038/ni.1863 (Epub 2010/04/21; PubMed PMID: 20404851)

    Article  CAS  PubMed  Google Scholar 

  11. Celhar T, Magalhaes R, Fairhurst AM (2012) TLR7 and TLR9 in SLE: when sensing self goes wrong. Immunol Res 53(1–3):58–77. https://doi.org/10.1007/s12026-012-8270-1 (Epub 2012/03/22; PubMed PMID: 22434514)

    Article  CAS  PubMed  Google Scholar 

  12. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB et al (2009) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97(25):13766–13771 (Epub 2000/11/30; 10.1073/pnas.250476497 PubMed PMID: 11095740; PubMed Central PMCID: PMCPMC17650)

    Article  Google Scholar 

  13. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR et al (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410(6832):1099–1103. https://doi.org/10.1038/35074106 (Epub 2001/04/27; PubMed PMID: 11323673)

    Article  CAS  PubMed  Google Scholar 

  14. Blasius AL, Beutler B (2010) Intracellular toll-like receptors. Immunity 32(3):305–315. https://doi.org/10.1016/j.immuni.2010.03.012 (Epub 2010/03/30 PubMed PMID: 20346772)

    Article  CAS  PubMed  Google Scholar 

  15. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413(6857):732–738. https://doi.org/10.1038/35099560 (Epub 2001/10/19; PubMed PMID: 11607032)

    Article  CAS  PubMed  Google Scholar 

  16. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S et al (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303(5663):1526–1529. https://doi.org/10.1126/science.1093620 (Epub 2004/02/21 PubMed PMID: 14976262)

    Article  CAS  PubMed  Google Scholar 

  17. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K et al (2002) Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nat Immunol 3(2):196–200. https://doi.org/10.1038/ni758 (Epub 2002/01/29; PubMed PMID: 11812998)

    Article  CAS  PubMed  Google Scholar 

  18. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H et al (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408(6813):740–745. https://doi.org/10.1038/35047123 (Epub 2000/12/29; PubMed PMID: 11130078)

    Article  CAS  PubMed  Google Scholar 

  19. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL, Serhan CN, Hayden MS et al (2005) TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308(5728):1626–1629. https://doi.org/10.1126/science.1109893 (Epub 2005/04/30; PubMed PMID: 15860593)

    Article  CAS  PubMed  Google Scholar 

  20. Koblansky AA, Jankovic D, Oh H, Hieny S, Sungnak W, Mathur R et al (2013) Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii. Immunity 38(1):119–130. https://doi.org/10.1016/j.immuni.2012.09.016 (Epub 2012/12/19; PubMed PMID: 23246311; PubMed Central PMCID: PMCPMC3601573)

    Article  CAS  PubMed  Google Scholar 

  21. Oldenburg M, Kruger A, Ferstl R, Kaufmann A, Nees G, Sigmund A et al (2012) TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science 337(6098):1111–1115. https://doi.org/10.1126/science.1220363 (Epub 2012/07/24; PubMed PMID: 22821982)

    Article  CAS  PubMed  Google Scholar 

  22. Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 279(17):17079–17084. https://doi.org/10.1074/jbc.M310859200 (Epub 2004/02/07 PubMed PMID: 14764599)

    Article  CAS  PubMed  Google Scholar 

  23. Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT et al (1999) Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 104(3):271–280. https://doi.org/10.1172/JCI6709 (Epub 1999/08/03; PubMed PMID: 10430608; PubMed Central PMCID: PMCPMC408420)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. O’Neill LA, Bowie AG (2007) The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 7(5):353–364. https://doi.org/10.1038/nri2079 (Epub 2007/04/26; PubMed PMID: 17457343)

    Article  CAS  PubMed  Google Scholar 

  25. Luo L, Lucas RM, Liu L, Stow JL (2019) Signalling, sorting and scaffolding adaptors for Toll-like receptors. J Cell Sci. https://doi.org/10.1242/jcs.239194 (Epub 2020/01/01; PubMed PMID: 31889021)

    Article  PubMed  Google Scholar 

  26. Berget SM, Moore C, Sharp PA (1977) Spliced segments at the 5’ terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci USA 74(8):3171–3175 (PubMed PMID: 269380; PubMed Central PMCID: PMCPMC431482)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chow LT, Gelinas RE, Broker TR, Roberts RJ (1977) An amazing sequence arrangement at the 5’ ends of adenovirus 2 messenger RNA. Cell 12(1):1–8 (PubMed PMID: 902310)

    Article  CAS  PubMed  Google Scholar 

  28. Douglas AG, Wood MJ (2011) RNA splicing: disease and therapy. Brief Funct Genomics 10(3):151–164. https://doi.org/10.1093/bfgp/elr020 (PubMed PMID: 21628314)

    Article  CAS  PubMed  Google Scholar 

  29. Lerner MR, Boyle JA, Mount SM, Wolin SL, Steitz JA (1980) Are snRNPs involved in splicing? Nature 283(5743):220–224 (PubMed PMID: 7350545)

    Article  CAS  PubMed  Google Scholar 

  30. Adamia S, Pilarski PM, Belch AR, Pilarski LM (2013) Aberrant splicing, hyaluronan synthases and intracellular hyaluronan as drivers of oncogenesis and potential drug targets. Curr Cancer Drug Targets 13(4):347–361 (PubMed PMID: 23517594)

    Article  CAS  PubMed  Google Scholar 

  31. Cooper TA, Wan L, Dreyfuss G (2009) RNA and disease. Cell 136(4):777–793. https://doi.org/10.1016/j.cell.2009.02.011 (PubMedPMID:19239895; PubMedCentralPMCID:PMCPMC2866189)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Padgett RA (2012) New connections between splicing and human disease. Trends Genet 28(4):147–154. https://doi.org/10.1016/j.tig.2012.01.001 (PubMedPMID:22397991; PubMedCentralPMCID:PMCPMC3319163)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wang GS, Cooper TA (2007) Splicing in disease: disruption of the splicing code and the decoding machinery. Nat Rev Genet 8(10):749–761. https://doi.org/10.1038/nrg2164 (PubMed PMID: 17726481)

    Article  CAS  PubMed  Google Scholar 

  34. Bernier FP, Caluseriu O, Ng S, Schwartzentruber J, Buckingham KJ, Innes AM et al (2012) Haploinsufficiency of SF3B4, a component of the pre-mRNA spliceosomal complex, causes Nager syndrome. Am J Hum Genet 90(5):925–933. https://doi.org/10.1016/j.ajhg.2012.04.004 (PubMedPMID:22541558;PubMedCentralPMCID:PMCPMC3376638)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gordon CT, Petit F, Oufadem M, Decaestecker C, Jourdain AS, Andrieux J et al (2012) EFTUD2 haploinsufficiency leads to syndromic oesophageal atresia. J Med Genet 49(12):737–746. https://doi.org/10.1136/jmedgenet-2012-101173 (PubMed PMID: 23188108)

    Article  CAS  PubMed  Google Scholar 

  36. Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L et al (1995) Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80(1):155–165 (PubMed PMID: 7813012)

    Article  CAS  PubMed  Google Scholar 

  37. Lines MA, Huang L, Schwartzentruber J, Douglas SL, Lynch DC, Beaulieu C et al (2012) Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly. Am J Hum Genet 90(2):369–377. https://doi.org/10.1016/j.ajhg.2011.12.023 (PubMedPMID:22305528; PubMedCentralPMCID:PMCPMC3276671)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Luquetti DV, Hing AV, Rieder MJ, Nickerson DA, Turner EH, Smith J et al (2013) “Mandibulofacial dysostosis with microcephaly” caused by EFTUD2 mutations: expanding the phenotype. Am J Med Genet A 161A(1):108–113. https://doi.org/10.1002/ajmg.a.35696 (PubMedPMID:23239648; PubMedCentralPMCID:PMCPMC3535578)

    Article  CAS  PubMed  Google Scholar 

  39. Mordes D, Luo X, Kar A, Kuo D, Xu L, Fushimi K et al (2006) Pre-mRNA splicing and retinitis pigmentosa. Mol Vis 12:1259–1271 (PubMed PMID: 17110909; PubMed Central PMCID: PMCPMC2683577)

    CAS  PubMed  Google Scholar 

  40. Neuenkirchen N, Chari A, Fischer U (2008) Deciphering the assembly pathway of Sm-class U snRNPs. FEBS Lett 582(14):1997–2003. https://doi.org/10.1016/j.febslet.2008.03.009 (PubMed PMID: 18348870)

    Article  CAS  PubMed  Google Scholar 

  41. Petit F, Escande F, Jourdain AS, Porchet N, Amiel J, Doray B et al (2014) Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause. Clin Genet 86(3):246–251. https://doi.org/10.1111/cge.12259 (PubMed PMID: 24003905)

    Article  CAS  PubMed  Google Scholar 

  42. Voigt C, Megarbane A, Neveling K, Czeschik JC, Albrecht B, Callewaert B et al (2013) Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations. Orphanet J Rare Dis 8:110. https://doi.org/10.1186/1750-1172-8-110 (PubMedPMID:23879989; PubMedCentralPMCID:PMCPMC3727992)

    Article  PubMed  PubMed Central  Google Scholar 

  43. Busch A, Hertel KJ (2012) Evolution of SR protein and hnRNP splicing regulatory factors. Wiley Interdiscip Rev RNA 3(1):1–12. https://doi.org/10.1002/wrna.100 (PubMedPMID:21898828;PubMedCentralPMCID:PMCPMC3235224)

    Article  CAS  PubMed  Google Scholar 

  44. Wang Z, Burge CB (2008) Splicing regulation: from a parts list of regulatory elements to an integrated splicing code. RNA 14(5):802–813. https://doi.org/10.1261/rna.876308 (PubMedPMID:18369186; PubMedCentralPMCID:PMCPMC2327353)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Wang Z, Xiao X, Van Nostrand E, Burge CB (2006) General and specific functions of exonic splicing silencers in splicing control. Mol Cell 23(1):61–70. https://doi.org/10.1016/j.molcel.2006.05.018 (PubMedPMID:16797197; PubMedCentralPMCID:PMCPMC1839040)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Ladd AN, Cooper TA (2002) Finding signals that regulate alternative splicing in the post-genomic era. Genome Biol 3(11):reviews0008 (PubMed PMID: 12429065; PubMed Central PMCID: PMCPMC244920)

    Article  PubMed  PubMed Central  Google Scholar 

  47. Rozovski U, Keating M, Estrov Z (2013) The significance of spliceosome mutations in chronic lymphocytic leukemia. Leuk Lymphoma 54(7):1364–1366. https://doi.org/10.3109/10428194.2012.742528 (Epub 2012/12/29; PubMed PMID: 23270583; PubMed Central PMCID: PMCPMC4176818)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Matera AG, Wang Z (2014) A day in the life of the spliceosome. Nat Rev Mol Cell Biol 15(2):108–121. https://doi.org/10.1038/nrm3742 (PubMedPMID:24452469; PubMedCentralPMCID:PMCPMC4060434)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Graubert TA, Shen D, Ding L, Okeyo-Owuor T, Lunn CL, Shao J et al (2011) Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet 44(1):53–57. https://doi.org/10.1038/ng.1031 (PubMedPMID:22158538; PubMedCentralPMCID:PMCPMC3247063)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L et al (2011) Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet 44(1):47–52. https://doi.org/10.1038/ng.1032 (PubMed PMID: 22158541)

    Article  CAS  PubMed  Google Scholar 

  51. Rosati E, Baldoni S, De Falco F, Del Papa B, Dorillo E, Rompietti C et al (2018) NOTCH1 aberrations in chronic lymphocytic leukemia. Front Oncol 8:229. https://doi.org/10.3389/fonc.2018.00229 (PubMed PMID: 29998084; PubMed Central PMCID: PMCPMC6030253)

    Article  PubMed  PubMed Central  Google Scholar 

  52. Expert-Bezancon A, Sureau A, Durosay P, Salesse R, Groeneveld H, Lecaer JP et al (2004) hnRNP A1 and the SR proteins ASF/SF2 and SC35 have antagonistic functions in splicing of beta-tropomyosin exon 6B. J Biol Chem 279(37):38249–38259. https://doi.org/10.1074/jbc.M405377200 (PubMed PMID: 15208309)

    Article  CAS  PubMed  Google Scholar 

  53. Sanford JR, Wang X, Mort M, Vanduyn N, Cooper DN, Mooney SD et al (2009) Splicing factor SFRS1 recognizes a functionally diverse landscape of RNA transcripts. Genome Res 19(3):381–394. https://doi.org/10.1101/gr.082503.108 (PubMedPMID:19116412; PubMedCentralPMCID:PMCPMC2661799)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Grigoryev YA. Post-Transcriptional Mechanisms of Gene Regulation and Information Control in Immunity. California: Proquest, Umi Dissertation Publishing; 2012. p. 284

  55. Ip JY, Tong A, Pan Q, Topp JD, Blencowe BJ, Lynch KW (2007) Global analysis of alternative splicing during T-cell activation. RNA 13(4):563–572. https://doi.org/10.1261/rna.457207 (PubMedPMID:17307815; PubMedCentralPMCID:PMCPMC1831861)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rodrigues R, Grosso AR, Moita L (2013) Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge. PLoS ONE 8(4):e61975. https://doi.org/10.1371/journal.pone.0061975 (Epub 2013/04/25; PubMed PMID: 23613991; PubMed Central PMCID: PMCPMC3629138)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C et al (2008) Alternative isoform regulation in human tissue transcriptomes. Nature 456(7221):470–476. https://doi.org/10.1038/nature07509 (PubMedPMID:18978772; PubMedCentralPMCID:PMCPMC2593745)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Nilsen TW, Graveley BR (2010) Expansion of the eukaryotic proteome by alternative splicing. Nature 463(7280):457–463. https://doi.org/10.1038/nature08909 (PubMedPMID:20110989; PubMedCentralPMCID:PMCPMC3443858)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Pan Q, Bakowski MA, Morris Q, Zhang W, Frey BJ, Hughes TR et al (2005) Alternative splicing of conserved exons is frequently species-specific in human and mouse. Trends Genet 21(2):73–77. https://doi.org/10.1016/j.tig.2004.12.004 (PubMed PMID: 15661351)

    Article  CAS  PubMed  Google Scholar 

  60. Bhatt DM, Pandya-Jones A, Tong AJ, Barozzi I, Lissner MM, Natoli G et al (2012) Transcript dynamics of proinflammatory genes revealed by sequence analysis of subcellular RNA fractions. Cell 150(2):279–290. https://doi.org/10.1016/j.cell.2012.05.043 (PubMed PMID: 22817891; PubMed Central PMCID: PMCPMC3405548)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hao S, Baltimore D (2013) RNA splicing regulates the temporal order of TNF-induced gene expression. Proc Natl Acad Sci USA 110(29):11934–11939. https://doi.org/10.1073/pnas.1309990110 (PubMed PMID: 23812748; PubMed Central PMCID: PMCPMC3718113)

    Article  PubMed  PubMed Central  Google Scholar 

  62. Wells CA, Chalk AM, Forrest A, Taylor D, Waddell N, Schroder K et al (2006) Alternate transcription of the Toll-like receptor signaling cascade. Genome Biol 7(2):R10. https://doi.org/10.1186/gb-2006-7-2-r10 (PubMedPMID:16507160;PubMedCentralPMCID:PMCPMC1431733)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Jaresova I, Rozkova D, Spisek R, Janda A, Brazova J, Sediva A (2007) Kinetics of Toll-like receptor-4 splice variants expression in lipopolysaccharide-stimulated antigen presenting cells of healthy donors and patients with cystic fibrosis. Microbes Infect 9(11):1359–1367. https://doi.org/10.1016/j.micinf.2007.06.009 (PubMed PMID: 17890129)

    Article  CAS  PubMed  Google Scholar 

  64. Iwami KI, Matsuguchi T, Masuda A, Kikuchi T, Musikacharoen T, Yoshikai Y (2000) Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccharide signaling. J Immunol 165(12):6682–6686. https://doi.org/10.4049/jimmunol.165.12.6682 (PubMed PMID: 11120784)

    Article  CAS  PubMed  Google Scholar 

  65. LeBouder E, Rey-Nores JE, Rushmere NK, Grigorov M, Lawn SD, Affolter M et al (2003) Soluble forms of Toll-like receptor (TLR)2 capable of modulating TLR2 signaling are present in human plasma and breast milk. J Immunol 171(12):6680–6689. https://doi.org/10.4049/jimmunol.171.12.6680 (Epub 2003/12/10; PubMed PMID: 14662871)

    Article  CAS  PubMed  Google Scholar 

  66. Song N, Li T (2018) Regulation of NLRP3 Inflammasome by Phosphorylation. Front Immunol 9:2305. https://doi.org/10.3389/fimmu.2018.02305 (Epub 2018/10/24; PubMed PMID: 30349539; PubMed Central PMCID: PMCPMC6186804)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Thygesen SJ, Sester DP, Cridland SO, Wilton SD, Stacey KJ (2016) Correcting the NLRP3 inflammasome deficiency in macrophages from autoimmune NZB mice with exon skipping antisense oligonucleotides. Immunol Cell Biol 94(5):520–524. https://doi.org/10.1038/icb.2016.3 (Epub 2016/02/03; PubMed PMID: 26833024)

    Article  CAS  PubMed  Google Scholar 

  68. Hoss F, Mueller JL, Rojas Ringeling F, Rodriguez-Alcazar JF, Brinkschulte R, Seifert G et al (2019) Alternative splicing regulates stochastic NLRP3 activity. Nat Commun 10(1):3238. https://doi.org/10.1038/s41467-019-11076-1 (Epub 2019/07/22; PubMed PMID: 31324763; PubMed Central PMCID: PMCPMC6642158)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cao X (2016) Self-regulation and cross-regulation of pattern-recognition receptor signalling in health and disease. Nat Rev Immunol 16(1):35–50. https://doi.org/10.1038/nri.2015.8 (Epub 2015/12/30; PubMed PMID: 26711677)

    Article  CAS  PubMed  Google Scholar 

  70. Scatizzi JC, Haraldsson MK, Pollard KM, Theofilopoulos AN, Kono DH (2012) The Lbw2 locus promotes autoimmune hemolytic anemia. J Immunol 188(7):3307–3314. https://doi.org/10.4049/jimmunol.1103561 (Epub 2012/03/01; PubMed PMID: 22371393; PubMed Central PMCID: PMCPMC3311724)

    Article  CAS  PubMed  Google Scholar 

  71. Borchers A, Ansari AA, Hsu T, Kono DH, Gershwin ME (2000) The pathogenesis of autoimmunity in New Zealand mice. Semin Arthritis Rheum 29(6):385–399. https://doi.org/10.1053/sarh.2000.7173 (Epub 2000/08/03; PubMed PMID: 10924025)

    Article  CAS  PubMed  Google Scholar 

  72. Gerstein MB, Rozowsky J, Yan KK, Wang D, Cheng C, Brown JB et al (2014) Comparative analysis of the transcriptome across distant species. Nature 512(7515):445–448. https://doi.org/10.1038/nature13424 (PubMedPMID:25164755; PubMedCentralPMCID:PMCPMC4155737)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wong JJ, Ritchie W, Ebner OA, Selbach M, Wong JW, Huang Y et al (2013) Orchestrated intron retention regulates normal granulocyte differentiation. Cell 154(3):583–595. https://doi.org/10.1016/j.cell.2013.06.052 (PubMed PMID: 23911323)

    Article  CAS  PubMed  Google Scholar 

  74. Edwards CR, Ritchie W, Wong JJ, Schmitz U, Middleton R, An X et al (2016) A dynamic intron retention program in the mammalian megakaryocyte and erythrocyte lineages. Blood 127(17):e24–e34. https://doi.org/10.1182/blood-2016-01-692764 (Epub 2016/03/11; PubMed PMID: 26962124; PubMed Central PMCID: PMCPMC4850870)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Middleton R, Gao D, Thomas A, Singh B, Au A, Wong JJ et al (2017) IRFinder: assessing the impact of intron retention on mammalian gene expression. Genome Biol 18(1):51. https://doi.org/10.1186/s13059-017-1184-4 (PubMedPMID:28298237; PubMedCentralPMCID:PMCPMC5353968)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Le Hir H, Gatfield D, Izaurralde E, Moore MJ (2001) The exon-exon junction complex provides a binding platform for factors involved in mRNA export and nonsense-mediated mRNA decay. EMBO J 20(17):4987–4997. https://doi.org/10.1093/emboj/20.17.4987 (PubMedPMID:11532962; PubMedCentralPMCID:PMCPMC125616)

    Article  PubMed  PubMed Central  Google Scholar 

  77. Le Hir H, Seraphin B (2008) EJCs at the heart of translational control. Cell 133(2):213–216. https://doi.org/10.1016/j.cell.2008.04.002 (PubMed PMID: 18423193)

    Article  CAS  PubMed  Google Scholar 

  78. Ishigaki Y, Li X, Serin G, Maquat LE (2001) Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 106(5):607–617 (PubMed PMID: 11551508)

    Article  CAS  PubMed  Google Scholar 

  79. Chiu SY, Lejeune F, Ranganathan AC, Maquat LE (2004) The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex. Genes Dev 18(7):745–754. https://doi.org/10.1101/gad.1170204 (PubMedPMID:15059963; PubMedCentralPMCID:PMCPMC387415)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Choe J, Oh N, Park S, Lee YK, Song OK, Locker N et al (2012) Translation initiation on mRNAs bound by nuclear cap-binding protein complex CBP80/20 requires interaction between CBP80/20-dependent translation initiation factor and eukaryotic translation initiation factor 3g. J Biol Chem 287(22):18500–18509. https://doi.org/10.1074/jbc.M111.327528 (PubMedPMID:22493286;PubMedCentralPMCID:PMCPMC3365721)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Anders KR, Grimson A, Anderson P (2003) SMG-5, required for C. elegans nonsense-mediated mRNA decay, associates with SMG-2 and protein phosphatase 2A. EMBO J 22(3):641–650. https://doi.org/10.1093/emboj/cdg056 (Epub 2003/01/30; PubMed PMID: 12554664; PubMed Central PMCID: PMCPMC140740)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Chiu SY, Serin G, Ohara O, Maquat LE (2003) Characterization of human Smg5/7a: a protein with similarities to Caenorhabditis elegans SMG5 and SMG7 that functions in the dephosphorylation of Upf1. RNA 9(1):77–87. https://doi.org/10.1261/rna.2137903 (Epub 2003/01/30; PubMed PMID: 12554878; PubMed Central PMCID: PMCPMC1370372)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Ohnishi T, Yamashita A, Kashima I, Schell T, Anders KR, Grimson A et al (2003) Phosphorylation of hUPF1 induces formation of mRNA surveillance complexes containing hSMG-5 and hSMG-7. Mol Cell 12(5):1187–1200 (PubMed PMID: 14636577)

    Article  CAS  PubMed  Google Scholar 

  84. Okada-Katsuhata Y, Yamashita A, Kutsuzawa K, Izumi N, Hirahara F, Ohno S (2012) N- and C-terminal Upf1 phosphorylations create binding platforms for SMG-6 and SMG-5:SMG-7 during NMD. Nucleic Acids Res 40(3):1251–1266. https://doi.org/10.1093/nar/gkr791 (Epub 2011/10/04; PubMed PMID: 21965535; PubMed Central PMCID: PMCPMC3273798)

    Article  CAS  PubMed  Google Scholar 

  85. Franks TM, Singh G, Lykke-Andersen J (2010) Upf1 ATPase-dependent mRNP disassembly is required for completion of nonsense- mediated mRNA decay. Cell 143(6):938–950. https://doi.org/10.1016/j.cell.2010.11.043 (Epub 2010/12/15; PubMed PMID: 21145460; PubMed Central PMCID: PMCPMC3357093)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Glavan F, Behm-Ansmant I, Izaurralde E, Conti E (2006) Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO J 25(21):5117–5125. https://doi.org/10.1038/sj.emboj.7601377 (Epub 2006/10/21; PubMed PMID: 17053788; PubMed Central PMCID: PMCPMC1630413)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Huntzinger E, Kashima I, Fauser M, Sauliere J, Izaurralde E (2008) SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan. RNA 14(12):2609–2617. https://doi.org/10.1261/rna.1386208 (Epub 2008/11/01; PubMed PMID: 18974281; PubMed Central PMCID: PMCPMC2590965)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schneider C, Leung E, Brown J, Tollervey D (2009) The N-terminal PIN domain of the exosome subunit Rrp44 harbors endonuclease activity and tethers Rrp44 to the yeast core exosome. Nucleic Acids Res 37(4):1127–1140. https://doi.org/10.1093/nar/gkn1020 (Epub 2009/01/09; PubMed PMID: 19129231; PubMed Central PMCID: PMCPMC2651783)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Eberle AB, Lykke-Andersen S, Muhlemann O, Jensen TH (2009) SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nat Struct Mol Biol 16(1):49–55. https://doi.org/10.1038/nsmb.1530 (Epub 2008/12/09; PubMed PMID: 19060897)

    Article  CAS  PubMed  Google Scholar 

  90. McIlwain DR, Pan Q, Reilly PT, Elia AJ, McCracken S, Wakeham AC et al (2010) Smg1 is required for embryogenesis and regulates diverse genes via alternative splicing coupled to nonsense-mediated mRNA decay. Proc Natl Acad Sci USA 107(27):12186–12191. https://doi.org/10.1073/pnas.1007336107 (PubMedPMID:20566848; PubMedCentralPMCID:PMCPMC2901484)

    Article  PubMed  PubMed Central  Google Scholar 

  91. Roberts TL, Ho U, Luff J, Lee CS, Apte SH, MacDonald KP et al (2013) Smg1 haploinsufficiency predisposes to tumor formation and inflammation. Proc Natl Acad Sci USA 110(4):E285–E294. https://doi.org/10.1073/pnas.1215696110 (PubMedPMID:23277562; PubMedCentralPMCID:PMCPMC3557096)

    Article  PubMed  Google Scholar 

  92. Singh G, Rebbapragada I, Lykke-Andersen J (2008) A competition between stimulators and antagonists of Upf complex recruitment governs human nonsense-mediated mRNA decay. PLoS Biol 6(4):e111. https://doi.org/10.1371/journal.pbio.0060111 (Epub 2008/05/02; PubMed PMID: 18447585; PubMed Central PMCID: PMCPMC2689706)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Ivanov PV, Gehring NH, Kunz JB, Hentze MW, Kulozik AE (2008) Interactions between UPF1, eRFs, PABP and the exon junction complex suggest an integrated model for mammalian NMD pathways. EMBO J 27(5):736–747. https://doi.org/10.1038/emboj.2008.17 (Epub 2008/02/08; PubMed PMID: 18256688; PubMed Central PMCID: PMCPMC2265754)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Gloggnitzer J, Akimcheva S, Srinivasan A, Kusenda B, Riehs N, Stampfl H et al (2014) Nonsense-mediated mRNA decay modulates immune receptor levels to regulate plant antibacterial defense. Cell Host Microbe 16(3):376–390. https://doi.org/10.1016/j.chom.2014.08.010 (Epub 2014/09/12; PubMed PMID: 25211079)

    Article  CAS  PubMed  Google Scholar 

  95. Garcia D, Garcia S, Voinnet O (2014) Nonsense-mediated decay serves as a general viral restriction mechanism in plants. Cell Host Microbe 16(3):391–402. https://doi.org/10.1016/j.chom.2014.08.001 (PubMed PMID: 25155460)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Balistreri G, Horvath P, Schweingruber C, Zund D, McInerney G, Merits A et al (2014) The host nonsense-mediated mRNA decay pathway restricts Mammalian RNA virus replication. Cell Host Microbe 16(3):403–411. https://doi.org/10.1016/j.chom.2014.08.007 (PubMed PMID: 25211080)

    Article  CAS  PubMed  Google Scholar 

  97. Labno A, Tomecki R, Dziembowski A (2016) Cytoplasmic RNA decay pathways—Enzymes and mechanisms. Biochim Biophys Acta 1863(12):3125–3147. https://doi.org/10.1016/j.bbamcr.2016.09.023 (PubMed PMID: 27713097)

    Article  CAS  PubMed  Google Scholar 

  98. Doidge R, Mittal S, Aslam A, Winkler GS (2012) Deadenylation of cytoplasmic mRNA by the mammalian Ccr4-Not complex. Biochem Soc Trans 40(4):896–901. https://doi.org/10.1042/BST20120074 (PubMed PMID: 22817755)

    Article  CAS  PubMed  Google Scholar 

  99. Wahle E, Winkler GS (2013) RNA decay machines: deadenylation by the Ccr4-not and Pan2-Pan3 complexes. Biochim Biophys Acta 1829(6–7):561–570. https://doi.org/10.1016/j.bbagrm.2013.01.003 (PubMed PMID: 23337855)

    Article  CAS  PubMed  Google Scholar 

  100. Coller JM, Gray NK, Wickens MP (1998) mRNA stabilization by poly(A) binding protein is independent of poly(A) and requires translation. Genes Dev 12(20):3226–3235. https://doi.org/10.1101/gad.12.20.3226 (Epub 1998/10/24; PubMed PMID: 9784497; PubMed Central PMCID: PMCPMC317214)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Brown JA, Roberts TL, Richards R, Woods R, Birrell G, Lim YC et al (2011) A novel role for hSMG-1 in stress granule formation. Mol Cell Biol 31(22):4417–4429. https://doi.org/10.1128/MCB.05987-11 (Epub 2011/09/14; PubMed PMID: 21911475; PubMed Central PMCID: PMCPMC3209244)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Caponigro G, Parker R (1995) Multiple functions for the poly(A)-binding protein in mRNA decapping and deadenylation in yeast. Genes Dev 9(19):2421–2432. https://doi.org/10.1101/gad.9.19.2421 (Epub 1995/10/01; PubMed PMID: 7557393)

    Article  CAS  PubMed  Google Scholar 

  103. Sheth U, Parker R (2003) Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300(5620):805–808. https://doi.org/10.1126/science.1082320 (Epub 2003/05/06; PubMed PMID: 12730603; PubMed Central PMCID: PMCPMC1876714)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Tharun S (2009) Lsm1-7-Pat1 complex: a link between 3’ and 5’-ends in mRNA decay? RNA Biol 6(3):228–232 (PubMed PMID: 19279404)

    Article  CAS  PubMed  Google Scholar 

  105. Miller JE, Reese JC (2012) Ccr4-Not complex: the control freak of eukaryotic cells. Crit Rev Biochem Mol Biol 47(4):315–333. https://doi.org/10.3109/10409238.2012.667214 (Epub 2012/03/16; PubMed PMID: 22416820; PubMed Central PMCID: PMCPMC3376659)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J et al (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433(7027):769–773. https://doi.org/10.1038/nature03315 (Epub 2005/02/03; PubMed PMID: 15685193)

    Article  CAS  PubMed  Google Scholar 

  107. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75(5):855–862. https://doi.org/10.1016/0092-8674(93)90530-4 (Epub 1993/12/03; PubMed PMID: 8252622)

    Article  CAS  PubMed  Google Scholar 

  108. Wu L, Fan J, Belasco JG (2006) MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA 103(11):4034–4039. https://doi.org/10.1073/pnas.0510928103 (Epub 2006/02/24; PubMed PMID: 16495412; PubMed Central PMCID: PMCPMC1449641)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Matsushita K, Takeuchi O, Standley DM, Kumagai Y, Kawagoe T, Miyake T et al (2009) Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458(7242):1185–1190. https://doi.org/10.1038/nature07924 (Epub 2009/03/27; PubMed PMID: 19322177)

    Article  CAS  PubMed  Google Scholar 

  110. Leppek K, Schott J, Reitter S, Poetz F, Hammond MC, Stoecklin G (2013) Roquin promotes constitutive mRNA decay via a conserved class of stem-loop recognition motifs. Cell 153(4):869–881. https://doi.org/10.1016/j.cell.2013.04.016 (Epub 2013/05/15; PubMed PMID: 23663784)

    Article  CAS  PubMed  Google Scholar 

  111. Murakawa Y, Hinz M, Mothes J, Schuetz A, Uhl M, Wyler E et al (2015) RC3H1 post-transcriptionally regulates A20 mRNA and modulates the activity of the IKK/NF-kappaB pathway. Nat Commun 6:7367. https://doi.org/10.1038/ncomms8367 (Epub 2015/07/15; PubMed PMID: 26170170; PubMed Central PMCID: PMCPMC4510711)

    Article  CAS  PubMed  Google Scholar 

  112. Tavernier SJ, Athanasopoulos V, Verloo P, Behrens G, Staal J, Bogaert DJ et al (2019) A human immune dysregulation syndrome characterized by severe hyperinflammation with a homozygous nonsense Roquin-1 mutation. Nat Commun 10(1):4779. https://doi.org/10.1038/s41467-019-12704-6 (Epub 2019/10/23; PubMed PMID: 31636267; PubMed Central PMCID: PMCPMC6803705)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Suzuki J, Ogawa M, Muto S, Itai A, Isobe M, Hirata Y et al (2011) Novel IkB kinase inhibitors for treatment of nuclear factor-kB-related diseases. Expert Opin Investig Drugs 20(3):395–405. https://doi.org/10.1517/13543784.2011.559162 (Epub 2011/02/15; PubMed PMID: 21314234)

    Article  CAS  PubMed  Google Scholar 

  114. Mino T, Murakawa Y, Fukao A, Vandenbon A, Wessels HH, Ori D et al (2015) Regnase-1 and roquin regulate a common element in inflammatory mRNAs by spatiotemporally distinct mechanisms. Cell 161(5):1058–1073. https://doi.org/10.1016/j.cell.2015.04.029 (Epub 2015/05/23; PubMed PMID: 26000482)

    Article  CAS  PubMed  Google Scholar 

  115. Mino T, Iwai N, Endo M, Inoue K, Akaki K, Hia F et al (2019) Translation-dependent unwinding of stem-loops by UPF1 licenses Regnase-1 to degrade inflammatory mRNAs. Nucleic Acids Res 47(16):8838–8859. https://doi.org/10.1093/nar/gkz628 (Epub 2019/07/23; PubMed PMID: 31329944; PubMed Central PMCID: PMCPMC7145602)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Kakiuchi N, Yoshida K, Uchino M, Kihara T, Akaki K, Inoue Y et al (2020) Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis. Nature 577(7789):260–265. https://doi.org/10.1038/s41586-019-1856-1 (Epub 2019/12/20; PubMed PMID: 31853061)

    Article  CAS  PubMed  Google Scholar 

  117. Nanki K, Fujii M, Shimokawa M, Matano M, Nishikori S, Date S et al (2020) Somatic inflammatory gene mutations in human ulcerative colitis epithelium. Nature 577(7789):254–259. https://doi.org/10.1038/s41586-019-1844-5 (Epub 2019/12/20; PubMed PMID: 31853059)

    Article  CAS  PubMed  Google Scholar 

  118. Nakatsuka Y, Yaku A, Handa T, Vandenbon A, Hikichi Y, Motomura Y et al (2021) Profibrotic function of pulmonary group 2 innate lymphoid cells is controlled by regnase-1. Eur Respir J 57(3):2000018. https://doi.org/10.1183/13993003.00018-2020 (Epub 2020/09/27; PubMed PMID: 32978308)

    Article  CAS  PubMed  Google Scholar 

  119. Yoshinaga M, Takeuchi O (2019) Post-transcriptional control of immune responses and its potential application. Clin Transl Immunol 8(6):e1063. https://doi.org/10.1002/cti2.1063 (Epub 2019/06/27; PubMed PMID: 31236273; PubMed Central PMCID: PMCPMC6580065)

    Article  CAS  Google Scholar 

  120. Khabar KS (2007) Rapid transit in the immune cells: the role of mRNA turnover regulation. J Leukoc Biol 81(6):1335–1344. https://doi.org/10.1189/jlb.0207109 (Epub 2007/04/03; PubMed PMID: 17400611; PubMed Central PMCID: PMCPMC7166898)

    Article  CAS  PubMed  Google Scholar 

  121. Shaw G, Kamen R (1986) A conserved AU sequence from the 3’ untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell 46(5):659–667. https://doi.org/10.1016/0092-8674(86)90341-7 (Epub 1986/08/29; PubMed PMID: 3488815)

    Article  CAS  PubMed  Google Scholar 

  122. Beisang D, Bohjanen PR (2012) Perspectives on the ARE as it turns 25 years old. Wiley Interdiscip Rev RNA 3(5):719–731. https://doi.org/10.1002/wrna.1125 (Epub 2012/06/27; PubMed PMID: 22733578; PubMed Central PMCID: PMCPMC4126804)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Ivanov P, Anderson P (2013) Post-transcriptional regulatory networks in immunity. Immunol Rev 253(1):253–272. https://doi.org/10.1111/imr.12051 (Epub 2013/04/05; PubMed PMID: 23550651; PubMed Central PMCID: PMCPMC6989036)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Wang J, Guo Y, Chu H, Guan Y, Bi J, Wang B (2013) Multiple functions of the RNA-binding protein HuR in cancer progression, treatment responses and prognosis. Int J Mol Sci 14(5):10015–10041. https://doi.org/10.3390/ijms140510015 (Epub 2013/05/15; PubMed PMID: 23665903; PubMed Central PMCID: PMCPMC3676826)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Hao S, Baltimore D (2009) The stability of mRNA influences the temporal order of the induction of genes encoding inflammatory molecules. Nat Immunol 10(3):281–288. https://doi.org/10.1038/ni.1699 (PubMedPMID:19198593; PubMedCentralPMCID:PMCPMC2775040)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Peng SS, Chen CY, Xu N, Shyu AB (1998) RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein. EMBO J 17(12):3461–3470. https://doi.org/10.1093/emboj/17.12.3461 (Epub 1998/06/17; PubMed PMID: 9628881; PubMed Central PMCID: PMCPMC1170682)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Chen YL, Huang YL, Lin NY, Chen HC, Chiu WC, Chang CJ (2006) Differential regulation of ARE-mediated TNFalpha and IL-1beta mRNA stability by lipopolysaccharide in RAW264.7 cells. Biochem Biophys Res Commun 346(1):160–168. https://doi.org/10.1016/j.bbrc.2006.05.093 (Epub 2006/06/09; PubMed PMID: 16759646)

    Article  CAS  PubMed  Google Scholar 

  128. Taylor GA, Carballo E, Lee DM, Lai WS, Thompson MJ, Patel DD et al (1996) A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4(5):445–454. https://doi.org/10.1016/s1074-7613(00)80411-2 (Epub 1996/05/01; PubMed PMID: 8630730)

    Article  CAS  PubMed  Google Scholar 

  129. Carballo E, Lai WS, Blackshear PJ (2000) Evidence that tristetraprolin is a physiological regulator of granulocyte-macrophage colony-stimulating factor messenger RNA deadenylation and stability. Blood 95(6):1891–1899 (Epub 2000/03/09; PubMed PMID: 10706852)

    Article  CAS  PubMed  Google Scholar 

  130. Lu JY, Sadri N, Schneider RJ (2006) Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Genes Dev 20(22):3174–3184. https://doi.org/10.1101/gad.1467606 (Epub 2006/11/07; PubMed PMID: 17085481; PubMed Central PMCID: PMCPMC1635151)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Sadri N, Schneider RJ (2009) Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease. J Invest Dermatol 129(3):657–670. https://doi.org/10.1038/jid.2008.298 (Epub 2008/10/03; PubMed PMID: 18830269; PubMed Central PMCID: PMCPMC4074411)

    Article  CAS  PubMed  Google Scholar 

  132. Stoecklin G, Stubbs T, Kedersha N, Wax S, Rigby WF, Blackwell TK et al (2004) MK2-induced tristetraprolin:14–3–3 complexes prevent stress granule association and ARE-mRNA decay. EMBO J 23(6):1313–1324. https://doi.org/10.1038/sj.emboj.7600163 (Epub 2004/03/12; PubMed PMID: 15014438; PubMed Central PMCID: PMCPMC381421)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Perry RP, Kelley DE, Friderici K, Rottman F (1975) The methylated constituents of L cell messenger RNA: evidence for an unusual cluster at the 5’ terminus. Cell 4(4):387–394 (PubMed PMID: 1168101)

    Article  CAS  PubMed  Google Scholar 

  134. Wei CM, Gershowitz A, Moss B (1975) Methylated nucleotides block 5’ terminus of HeLa cell messenger RNA. Cell 4(4):379–386 (PubMed PMID: 164293)

    Article  CAS  PubMed  Google Scholar 

  135. Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR (2012) Comprehensive analysis of mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell 149(7):1635–1646. https://doi.org/10.1016/j.cell.2012.05.003 (PubMedPMID:22608085; PubMedCentralPMCID:PMCPMC3383396)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20. https://doi.org/10.1016/j.cell.2004.12.035 (PubMed PMID: 15652477)

    Article  CAS  PubMed  Google Scholar 

  137. Meyer KD, Jaffrey SR (2017) Rethinking m(6)A readers, writers, and erasers. Annu Rev Cell Dev Biol 33:319–342. https://doi.org/10.1146/annurev-cellbio-100616-060758 (Epub 2017/08/02; PubMed PMID: 28759256; PubMed Central PMCID: PMCPMC5963928)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Liu J, Yue Y, Han D, Wang X, Fu Y, Zhang L et al (2014) A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation. Nat Chem Biol 10(2):93–95. https://doi.org/10.1038/nchembio.1432 (PubMedPMID:24316715; PubMedCentralPMCID:PMCPMC3911877)

    Article  CAS  PubMed  Google Scholar 

  139. Zheng G, Dahl JA, Niu Y, Fedorcsak P, Huang CM, Li CJ et al (2013) ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell 49(1):18–29. https://doi.org/10.1016/j.molcel.2012.10.015 (PubMed PMID: 23177736; PubMed Central PMCID: PMCPMC3646334)

    Article  CAS  PubMed  Google Scholar 

  140. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y et al (2011) N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol 7(12):885–887. https://doi.org/10.1038/nchembio.687 (Epub 2011/10/18; PubMed PMID: 22002720; PubMed Central PMCID: PMCPMC3218240)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Zaccara S, Jaffrey SR (2020) A unified model for the function of YTHDF proteins in regulating m(6)A-modified mRNA. Cell 181(7):1582-1595.e18. https://doi.org/10.1016/j.cell.2020.05.012 (Epub 2020/06/04; PubMed PMID: 32492408; PubMed Central PMCID: PMCPMC7508256)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Bokar JA, Shambaugh ME, Polayes D, Matera AG, Rottman FM (1997) Purification and cDNA cloning of the AdoMet-binding subunit of the human mRNA (N6-adenosine)-methyltransferase. RNA 3(11):1233–1247 (PubMed PMID: 9409616; PubMed Central PMCID: PMCPMC1369564)

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Ping XL, Sun BF, Wang L, Xiao W, Yang X, Wang WJ et al (2014) Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res 24(2):177–189. https://doi.org/10.1038/cr.2014.3 (PubMedPMID:24407421; PubMedCentralPMCID:PMCPMC3915904)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Schwartz S, Mumbach MR, Jovanovic M, Wang T, Maciag K, Bushkin GG et al (2014) Perturbation of m6A writers reveals two distinct classes of mRNA methylation at internal and 5’ sites. Cell Rep 8(1):284–296. https://doi.org/10.1016/j.celrep.2014.05.048 (PubMedPMID:24981863; PubMedCentralPMCID:PMCPMC4142486)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Patil DP, Chen CK, Pickering BF, Chow A, Jackson C, Guttman M et al (2016) m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 537(7620):369–373. https://doi.org/10.1038/nature19342 (PubMedPMID:27602518; PubMedCentralPMCID:PMCPMC5509218)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Pendleton KE, Chen B, Liu K, Hunter OV, Xie Y, Tu BP et al (2017) The U6 snRNA m(6)A methyltransferase METTL16 regulates SAM synthetase intron retention. Cell 169(5):824-835.e14. https://doi.org/10.1016/j.cell.2017.05.003 (PubMed PMID: 28525753; PubMed Central PMCID: PMCPMC5502809)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Roundtree IA, Evans ME, Pan T, He C (2017) Dynamic RNA modifications in gene expression regulation. Cell 169(7):1187–1200. https://doi.org/10.1016/j.cell.2017.05.045 (Epub 2017/06/18; PubMed PMID: 28622506; PubMed Central PMCID: PMCPMC5657247)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Patil DP, Pickering BF, Jaffrey SR (2018) Reading m(6)A in the transcriptome: m(6)A-binding proteins. Trends Cell Biol 28(2):113–127. https://doi.org/10.1016/j.tcb.2017.10.001 (Epub 2017/11/07; PubMed PMID: 29103884; PubMed Central PMCID: PMCPMC5794650)

    Article  CAS  PubMed  Google Scholar 

  149. Alarcon CR, Goodarzi H, Lee H, Liu X, Tavazoie S, Tavazoie SF (2015) HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell 162(6):1299–1308. https://doi.org/10.1016/j.cell.2015.08.011 (PubMedPMID:26321680; PubMedCentralPMCID:PMCPMC4673968)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Wu B, Su S, Patil DP, Liu H, Gan J, Jaffrey SR et al (2018) Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1. Nat Commun 9(1):420. https://doi.org/10.1038/s41467-017-02770-z (Epub 2018/01/31; PubMed PMID: 29379020; PubMed Central PMCID: PMCPMC5789076)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Winkler R, Gillis E, Lasman L, Safra M, Geula S, Soyris C et al (2019) Publisher Correction: m6A modification controls the innate immune response to infection by targeting type I interferons. Nat Immunol 20(2):243. https://doi.org/10.1038/s41590-019-0314-4 (Epub 2019/01/13; PubMed PMID: 30635652)

    Article  CAS  PubMed  Google Scholar 

  152. Rubio RM, Depledge DP, Bianco C, Thompson L, Mohr I (2018) RNA m(6) A modification enzymes shape innate responses to DNA by regulating interferon beta. Genes Dev 32(23–24):1472–1484. https://doi.org/10.1101/gad.319475.118 (Epub 2018/11/23; PubMed PMID: 30463905; PubMed Central PMCID: PMCPMC6295168)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Hemadou A, Giudicelli V, Smith ML, Lefranc MP, Duroux P, Kossida S et al (2017) Pacific biosciences sequencing and IMGT/HighV-QUEST analysis of full-length single chain fragment variable from an in vivo selected phage-display combinatorial library. Front Immunol 8:1796. https://doi.org/10.3389/fimmu.2017.01796 (PubMed PMID: 29326697; PubMed Central PMCID: PMCPMC5742356)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Mailer RK, Joly AL, Liu S, Elias S, Tegner J, Andersson J (2015) IL-1beta promotes Th17 differentiation by inducing alternative splicing of FOXP3. Sci Rep 5:14674. https://doi.org/10.1038/srep14674 (PubMedPMID:26441347; PubMedCentralPMCID:PMCPMC4593960)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Feng Z, Li Q, Meng R, Yi B, Xu Q (2018) METTL3 regulates alternative splicing of MyD88 upon the lipopolysaccharide-induced inflammatory response in human dental pulp cells. J Cell Mol Med 22(5):2558–2568. https://doi.org/10.1111/jcmm.13491 (PubMedPMID:29502358; PubMedCentralPMCID:PMCPMC5908103)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Bacchetta R, Barzaghi F, Roncarolo MG (2016) From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation. Ann N Y Acad Sci. https://doi.org/10.1111/nyas.13011 (PubMed PMID: 26918796)

    Article  PubMed  Google Scholar 

  157. Shaheen R, Anazi S, Ben-Omran T, Seidahmed MZ, Caddle LB, Palmer K et al (2016) Mutations in SMG9, encoding an essential component of nonsense-mediated decay machinery, cause a multiple congenital anomaly syndrome in humans and mice. Am J Hum Genet 98(4):643–652. https://doi.org/10.1016/j.ajhg.2016.02.010 (PubMedPMID:27018474; PubMedCentralPMCID:PMCPMC4833216)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Pellagatti A, Boultwood J (2017) Splicing factor gene mutations in the myelodysplastic syndromes: impact on disease phenotype and therapeutic applications. Adv Biol Regul 63:59–70. https://doi.org/10.1016/j.jbior.2016.08.001 (PubMed PMID: 27639445)

    Article  CAS  PubMed  Google Scholar 

  159. Yanagi T, Mizuochi T, Takaki Y, Eda K, Mitsuyama K, Ishimura M et al (2016) Novel exonic mutation inducing aberrant splicing in the IL10RA gene and resulting in infantile-onset inflammatory bowel disease: a case report. BMC Gastroenterol 16:10. https://doi.org/10.1186/s12876-016-0424-5 (PubMedPMID:26822028; PubMedCentralPMCID:PMCPMC4730728)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Mora M, Hanzu FA, Pradas-Juni M, Aranda GB, Halperin I, Puig-Domingo M et al (2014) New splice site acceptor mutation in AIRE gene in autoimmune polyendocrine syndrome type 1. PLoS One 9(7):e101616. https://doi.org/10.1371/journal.pone.0101616 (PubMedPMID:24988226; PubMedCentralPMCID:PMCPMC4079332)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Kim YG, Kim M, Kang JH, Kim HJ, Park JW, Lee JM et al (2016) Transcriptome sequencing of gingival biopsies from chronic periodontitis patients reveals novel gene expression and splicing patterns. Hum Genomics 10(1):28. https://doi.org/10.1186/s40246-016-0084-0 (PubMedPMID:27531006; PubMedCentralPMCID:PMCPMC4988046)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Duplantier JE, Seyama K, Day NK, Hitchcock R, Nelson RP Jr, Ochs HD et al (2001) Immunologic reconstitution following bone marrow transplantation for X-linked hyper IgM syndrome. Clin Immunol 98(3):313–318. https://doi.org/10.1006/clim.2000.4994 (PubMed PMID: 11237554)

    Article  CAS  PubMed  Google Scholar 

  163. Salzer E, Santos-Valente E, Klaver S, Ban SA, Emminger W, Prengemann NK et al (2013) B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta. Blood 121(16):3112–3116. https://doi.org/10.1182/blood-2012-10-460741 (PubMedPMID:23319571; PubMedCentralPMCID:PMCPMC3630826)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Hashimoto M, Nagao JI, Ikezaki S, Tasaki S, Arita-Morioka KI, Narita Y et al (2017) Identification of a novel alternatively spliced form of inflammatory regulator SWAP-70-like adapter of T cells. Int J Inflam 2017:1324735. https://doi.org/10.1155/2017/1324735 (PubMedPMID:28523202; PubMedCentralPMCID:PMCPMC5421089)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Banks L. The Role of the Akt2 Isoform in Th17 Differentiation in Vitro and Peripheral Cd4 T Cell Immune Responses in Vivo. Publicly Accessible Penn Dissertations. 2014;1203

  166. Bihl MP, Heinimann K, Rudiger JJ, Eickelberg O, Perruchoud AP, Tamm M et al (2002) Identification of a novel IL-6 isoform binding to the endogenous IL-6 receptor. Am J Respir Cell Mol Biol 27(1):48–56. https://doi.org/10.1165/ajrcmb.27.1.4637 (PubMed PMID: 12091245)

    Article  CAS  PubMed  Google Scholar 

  167. Heinhuis B, Plantinga TS, Semango G, Kusters B, Netea MG, Dinarello CA et al (2016) Alternatively spliced isoforms of IL-32 differentially influence cell death pathways in cancer cell lines. Carcinogenesis 37(2):197–205. https://doi.org/10.1093/carcin/bgv172 (PubMed PMID: 26678222)

    Article  CAS  PubMed  Google Scholar 

  168. Lee TL, Chang ML, Lin YJ, Tsai MH, Chang YH, Chuang CM et al (2015) An alternatively spliced IL-15 isoform modulates abrasion-induced keratinocyte activation. J Invest Dermatol 135(5):1329–1337. https://doi.org/10.1038/jid.2015.17 (PubMed PMID: 25615554)

    Article  CAS  PubMed  Google Scholar 

  169. Luzina IG, Lockatell V, Todd NW, Keegan AD, Hasday JD, Atamas SP (2011) Splice isoforms of human interleukin-4 are functionally active in mice in vivo. Immunology 132(3):385–393. https://doi.org/10.1111/j.1365-2567.2010.03393.x (PubMedPMID:21219317; PubMedCentralPMCID:PMCPMC3044904)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Hong C, Luckey MA, Ligons DL, Waickman AT, Park JY, Kim GY et al (2014) Activated T cells secrete an alternatively spliced form of common gamma-chain that inhibits cytokine signaling and exacerbates inflammation. Immunity 40(6):910–923. https://doi.org/10.1016/j.immuni.2014.04.020 (PubMedPMID:24909888; PubMedCentralPMCID:PMCPMC4143255)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Uda Y. Ho, Alexander James, Paul De Souza and Tara L. Roberts for their input on the manuscript figures and text.

Funding

There is no funding support in this review paper.

Author information

Authors and Affiliations

  1. Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia

    Hui-Chi Lai, Alexander James, Paul De Souza & Tara L. Roberts

  2. South West Sydney Clinical School, UNSW Australia, Liverpool, NSW, Australia

    Hui-Chi Lai & Tara L. Roberts

  3. School of Biomedical Sciences, Faculty of Medicine, University of Queensland, Brisbane, Australia

    Uda Y. Ho

  4. School of Medicine, University of Wollongong, Wollongong, NSW, Australia

    Paul De Souza

  5. School of Medicine, Western Sydney University, Macarthur, NSW, Australia

    Paul De Souza & Tara L. Roberts

Authors
  1. Hui-Chi Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Uda Y. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander James
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul De Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tara L. Roberts
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H-CL wrote the manuscript with feedback from all authors. UYH, AJ, PDS and TLR gave their comments and suggestions to the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hui-Chi Lai.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This review paper required no ethics approval.

Consent for publication

All authors have read the manuscript and agreed to give their consent for the publication of identifiable details and information to be published in the above Journal of Cellular and molecular life science.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lai, HC., Ho, U.Y., James, A. et al. RNA metabolism and links to inflammatory regulation and disease. Cell. Mol. Life Sci. 79, 21 (2022). https://doi.org/10.1007/s00018-021-04073-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00018-021-04073-5

Keywords

Search

Navigation