ncRNA

The discovery of microRNAs (miRNAs) has added a new player to the regulation of gene expression. With the increasing number of molecular species involved in gene regulatory networks, it is hard to obtain an intuitive understanding of network dynamics. Mathematical modelling can help dissecting the role of miRNAs in gene regulatory networks, and we shall here review the most recent developments that utilise different mathematical modelling approaches to provide quantitative insights into the function of miRNAs in the regulation of gene expression. Key miRNA regulation features that have been elucidated via modelling include: (i) the role of miRNA-mediated feedback and feedforward loops in fine-tuning of gene expression; (ii) the miRNA–target interaction properties determining the effectiveness of miRNA-mediated gene repression; and (iii) the competition for shared miRNAs leading to the cross-regulation of genes. However, there is still lack of mechanistic understanding of many other properties of miRNA regulation like unconventional miRNA–target interactions, miRNA regulation at different sub-cellular locations and functional miRNA variant, which will need future modelling efforts to deal with. This review provides an overview of recent developments and challenges in this field.

The Rfam database is a collection of RNA families in which each family is represented by a multiple sequence alignment, a consensus secondary structure, and a covariance model. In this paper we introduce Rfam release 13.0, which switches to a new genome-centric approach that annotates a non-redundant set of reference genomes with RNA families. We describe new web interface features including faceted text search and R-scape secondary structure visualizations. We discuss a new literature cu-ration workflow and a pipeline for building families based on RNAcentral. There are 236 new families in release 13.0, bringing the total number of families to 2687. The Rfam website is http://rfam.org.

The pathogenesis of osteoporosis is multifactorial and is the consequence of genetic, hormonal and lifestyle factors. Epigenetics, including noncoding RNAs deregulation, represents a link between susceptibility to develop the disease and environmental in uences. The majority of studies investigated the expression of ncRNAs in osteoporosis patients; however, very few information is available on their genetic variability. In this review, we focus on two classes of ncRNAs: microRNAs and long noncoding RNAs. We summarize recent ndings on how polymorphisms in miRNAs and long noncoding RNAs (lncRNAs) can perturb the lncRNA/miRNA/mRNA axis and may be involved in osteoporosis clinical outcome. We also provide a general overview on databases and bioinformatic tools useful for associating miRNAs and lncRNAs variability with complex genetic diseases. The Encyclopaedia of DNA Elements (ENCODE) project has revealed that-considering the annotated exons in the human genome-less than 2% of the genome encodes for protein-coding RNAs [1,2]. This discovery raised questions about the functional utility of all the remaining nonprotein-coding transcripts in the human genome. Recently, it has emerged that noncoding RNAs (ncRNAs) genes are not junk [3], but play important roles in multiple biological processes by directly or indirectly interfering with gene expression; the deregulation of ncRNAs is associated with a variety of diseases and metabolic disorders including osteoporosis (OP) [4,5]. OP is a skeletal disorder characterized by compromised bone strength, a low bone mineral density (BMD) and an increased risk of fracture and bone fragility [6-8]. The pathogenic mechanism is complex and is triggered by a combination of genetic, metabolic and environmental factors [9]. The genetic component plays a pivotal role in OP development since BMD heritability has been estimated from 50 to 85% and, more variably, fracture heritability ranged from 25 to 68% [10]. Genome-wide association studies (GWAS) have contributed to reveal genetic variants correlated with higher risk of OP development. More than 500 loci have been associated with BMD through a recent large-scale GWAS [11,12] and 13 loci have been found to be highly associated with an increased risk of fracture [12]. To date, genes identified through GWAS studies are mainly involved in osteoblasts and osteoclasts biogenesis and activity, such as members of the beta-catenin/Wnt and osteoprotegerin pathways [13] implicated in ossification processes and bone strength regulation [12,14]. Interestingly, data from GWAS catalogues have indicated that most of genetic variants associated with BMD and osteoporotic fractures were in noncoding regions of the genome, raising the possibility that these polymorphisms may exert regulatory effects on the bone-related genes expression [15]. Noncoding single nucleotide polymorphisms (ncSNPs) can be located in promoters, enhancers, 5 and 3 UTR gene regions or even in ncRNA Epigenomics (Epub ahead of print)

Background: Our previous study found that more than 500 transcripts significantly increased in abundance in the zebrafish and mouse several hours to days postmortem relative to live controls. The current literature suggests that most mRNAs are post-transcriptionally regulated in stressful conditions. We rationalized that the postmortem transcripts must contain sequence features (3-to 9-mers) that are unique from those in the rest of the transcriptome and that these features putatively serve as binding sites for proteins and/or non-coding RNAs involved in post-transcriptional regulation.

Background Bovine milk contains extracellular vesicles (EVs) that play a role in cellular communication, acting in either an autocrine, paracrine, or an exocrine manner. The unique properties of the EVs protect the cargo against degradation. We profiled the ncRNAs (non-coding RNA) present in the EVs from seven dairy products - raw whole milk, heat-treated skim milk, homogenized heat-treated skim milk, pasteurized homogenized skim milk, pasteurized heavy whipping cream, sweet cream buttermilk and cultured buttermilk with four replicates each, obtained at different processing steps from a commercial dairy plant. EVs and their cargo were extracted by using a validated commercial kit that has been shown to be efficient and specific for EVs. Further, to find the annotation of ncRNAs, we probed bovine and other organism repositories(such as miRBase, miRTarBase, Ensemble) to find homolog ncRNA annotation in case the annotations of ncRNA are not available in Bos Taurus database. Results Spe...

The pathogenesis of osteoporosis is multifactorial and is the consequence of genetic, hormonal and lifestyle factors. Epigenetics, including noncoding RNA (ncRNA) deregulation, represents a link between susceptibility to develop the disease and environmental influences. The majority of studies investigated the expression of ncRNAs in osteoporosis patients; however, very little information is available on their genetic variability. In this review, we focus on two classes of ncRNAs: miRNAs and long noncoding RNAs (lncRNAs). We summarize recent findings on how polymorphisms in miRNAs and lncRNAs can perturb the lncRNA/miRNA/mRNA axis and may be involved in osteoporosis clinical outcome. We also provide a general overview on databases and bioinformatic tools useful for associating miRNAs and lncRNAs variability with complex genetic diseases.

The brain is the central organ of the body's response to and perception of stress. Both the juvenile and the adult brain show a significant capacity for lasting physiological, structural and behavioral plasticity as a consequence of stress exposure. The hypothesis that epigenetic mechanisms might lie behind the lasting effects of stress upon the brain has proven a fruitful one. In this review, we examine the growing literature showing that stress has a direct impact on epigenetic marks at all life history stages thus far examined and how, in turn, epigenetic mechanisms play a role in altering stress responsiveness, anxiety and brain plasticity across the lifespan and beyond to succeeding generations. In addition, we will examine our own recent findings that stress interacts with the epigenome to regulate the expression of transposable elements in a regionally specific fashion, a finding with significant implications for a portion of the genome which is tenfold larger than that o...

Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By acces...