Abstract
BackgroundOur understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). However, the function of lncRNAs in gene regulation is not well understood; moreover, finding conserved lncRNA across species is a challenging task. Therefore, we propose a novel approach to identify conserved lncRNAs and functionally annotate these molecules.ResultsIn this study, we exploited existing myogenic transcriptome data and identified conserved lncRNAs in mice and humans. We identified the lncRNAs expressing differentially between the early and later stages of muscle development. Differential expression of these lncRNAs was confirmed experimentally in cultured mouse muscle C2C12 cells. We utilized the three-dimensional architecture of the genome and identified topologically associated domains for these lncRNAs. Additionally, we correlated the expression of genes in domains for functional annotation of these trans-lncRNAs in myogenesis. Using this approach, we identified conserved lncRNAs in myogenesis and functionally annotated them.ConclusionsWith this novel approach, we identified the conserved lncRNAs in myogenesis in humans and mice and functionally annotated them. The method identified a large number of lncRNAs are involved in myogenesis. Further studies are required to investigate the reason for the conservation of the lncRNAs in human and mouse while their sequences are dissimilar. Our approach can be used to identify novel lncRNAs conserved in different species and functionally annotated them.
Highlights
Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed
We functionally characterized long non-coding RNA (lncRNA) by examining the gene ontology of neighbouring genes, as well as by investigating the ontologies of genes in close vicinity in three-dimensional space. Some of these identified lncRNAs were experimentally validated in C2C12 cells, and the results revealed that the computationally identified lncRNAs are differentially expressed in these cells
Identification of lncRNAs involved in mouse myogenesis To identify lncRNAs in the mouse skeletal muscle system, we used Trapnell et al.’s C2C12 myoblast and early myotube (3 days after differentiation) deep RNA sequencing (RNA-Seq) data [35]
Summary
Our understanding of genome regulation is ever-evolving with the continuous discovery of new modes of gene regulation, and transcriptomic studies of mammalian genomes have revealed the presence of a considerable population of non-coding RNA molecules among the transcripts expressed. One such non-coding RNA molecule is long non-coding RNA (lncRNA). Similar to messenger RNAs, lncRNAs contain a 5′7-methylguanosine cap and a 3′ poly(A) tail; lncRNAs lack coding potential This new class of genes has recently been identified in various tissues [7,8,9,10].
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