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      Long non-coding RNA: its evolutionary relics and biological implications in mammals: a review

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          Abstract

          The central dogma of gene expression propounds that DNA is transcribed to mRNA and finally gets translated into protein. Only 2–3% of the genomic DNA is transcribed to protein-coding mRNA. Interestingly, only a further minuscule part of genomic DNA encodes for long non-coding RNAs (lncRNAs) which are characteristically more than 200 nucleotides long and can be transcribed from both protein-coding (e.g. H19 and TUG1) as well as non-coding DNA by RNA polymerase II. The lncRNAs do not have open reading frames (with some exceptions), 3`-untranslated regions (3’-UTRs) and necessarily these RNAs lack any translation-termination regions, however, these can be spliced, capped and polyadenylated as mRNA molecules. The flexibility of lncRNAs confers them specific 3D-conformations that eventually enable the lncRNAs to interact with proteins, DNA or other RNA molecules via base pairing or by forming networks. The lncRNAs play a major role in gene regulation, cell differentiation, cancer cell invasion and metastasis and chromatin remodeling. Deregulation of lncRNA is also responsible for numerous diseases in mammals. Various studies have revealed their significance as biomarkers for prognosis and diagnosis of cancer. The aim of this review is to overview the salient features, evolution, biogenesis and biological importance of these molecules in the mammalian system.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.

            Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression. Copyright (c) 2010 Elsevier Inc. All rights reserved.
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              The H19 lincRNA is a developmental reservoir of miR-675 which suppresses growth and Igf1r

              The H19 large intergenic noncoding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extraembryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded within H19’s first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extraembryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth promoting Insulin-like growth factor 1 receptor (Igf1r). Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress response RNA binding protein HuR. These results suggest that H19’s main physiological role is in limiting growth of the placenta prior to birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.
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                Author and article information

                Contributors
                jasdeep7dhanoa@gmail.com
                sethi116@gmail.com
                ramneek.verma@gmail.com
                drarora2003@gmail.com
                csmbioinfo@gmail.com
                Journal
                J Anim Sci Technol
                J Anim Sci Technol
                Journal of Animal Science and Technology
                BioMed Central (London )
                2055-0391
                25 October 2018
                25 October 2018
                2018
                : 60
                : 25
                Affiliations
                ISNI 0000 0004 1808 3035, GRID grid.411890.5, School of Animal Biotechnology, , Guru Angad Dev Veterinary and Animal Sciences University, ; Ludhiana, Punjab India
                Author information
                http://orcid.org/0000-0002-4545-4204
                Article
                183
                10.1186/s40781-018-0183-7
                6201556
                30386629
                322cb727-f69b-4528-a98a-aab06b4d6931
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 23 August 2018
                : 5 October 2018
                Funding
                Funded by: Department of Biology, Indiana State University (US)
                Award ID: AAB-009
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2018

                long non-coding rna,biogenesis,disease biomarker,evolution,mammals

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