Abstract
A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced a major shift in our understanding of gene and genome regulation and structure. It became apparent that lncRNAs regulate gene expression through several mechanisms. These RNAs function as transcriptional or post-transcriptional regulators through binding to histone-modifying complexes, to DNA, to transcription factors and other DNA binding proteins, to RNA polymerase II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the lncRNA transcription itself rather than the lncRNA product appears to be regulatory. In this review, we highlight studies identifying lncRNAs in the homeostasis of various cell and tissue types or demonstrating their effects in the expression of protein-coding or other non-coding RNA genes.
Highlights
Until a few years ago, non-coding RNAs were an unexplored component of the transcriptome considered as transcriptional noise
Regulating homeostasis of the intestinal epithelial barrier, the long non-coding RNAs (lncRNAs) H19 may act as a ceRNA, competing with the miR-874, a microRNA which supresses the expression of the aquaporin-3 gene (AQP3) by binding to the 30 untranslated region (UTR) of its messenger RNAs (mRNA)
A feedback loop has been identified within the NANCI-Nkx2.1 gene duplex that is critical for buffering the expression of the transcription factor Nkx2.1, maintaining lung epithelial cell identity during development and postnatal tissue homeostasis: while Nkx2.1 directly inhibits the expression of the lncRNA NANCI (Nkx2.1-associated noncoding intergenic RNA, called LL18), NANCI acts in cis to promote Nkx2.1 transcription [139,140]
Summary
Until a few years ago, non-coding RNAs (ncRNA) were an unexplored component of the transcriptome considered as transcriptional noise. Long non-coding RNA genes may present tissue- and cell-specific expression and differ from mRNA genes by having longer and fewer exons [3]. (b8) modulating alternative splicing of primary transcripts; (b9) as competing endogenous RNA (ceRNA), serving as a sponge for microRNAs (miRNAs), blocking their effect; (b10) targeting proteins, forming molecular complexes which can block or induce functional effects, or even alter their location in the cell; (b11) targeting messenger RNAs (mRNAs), inhibiting their translation in ribosomes. LncRNAs are known to be involved in gene expression regulation—at the transcriptional and post-transcriptional levels, by epigenetic or other mechanisms, such as interfering with the recruitment of RNA polymerase II or inducing chromatin remodeling They participate in genomic imprinting; in nuclear and cytoplasmic trafficking; in protein localization and activity; and in interaction with miRNAs, among other processes (reviewed in [12]). We present the information by cell or tissue type throughout this review
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