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      LncRNA Structural Characteristics in Epigenetic Regulation

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          Abstract

          The rapid development of new generation sequencing technology has deepened the understanding of genomes and functional products. RNA-sequencing studies in mammals show that approximately 85% of the DNA sequences have RNA products, for which the length greater than 200 nucleotides (nt) is called long non-coding RNAs (lncRNA). LncRNAs now have been shown to play important epigenetic regulatory roles in key molecular processes, such as gene expression, genetic imprinting, histone modification, chromatin dynamics, and other activities by forming specific structures and interacting with all kinds of molecules. This paper mainly discusses the correlation between the structure and function of lncRNAs with the recent progress in epigenetic regulation, which is important to the understanding of the mechanism of lncRNAs in physiological and pathological processes.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Miao-Chih Tsai, Ohad Manor, Yue Wan … (2010)
          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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            Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

            Q. Chen, M. Yan, Z. Cao … (2016)
            Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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              Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs

              Mitchell Guttman, Manuel Garber, Joshua Levin … (2010)
              RNA-Seq provides an unbiased way to study a transcriptome, including both coding and non-coding genes. To date, most RNA-Seq studies have critically depended on existing annotations, and thus focused on expression levels and variation in known transcripts. Here, we present Scripture, a method to reconstruct the transcriptome of a mammalian cell using only RNA-Seq reads and the genome sequence. We apply it to mouse embryonic stem cells, neuronal precursor cells, and lung fibroblasts to accurately reconstruct the full-length gene structures for the vast majority of known expressed genes. We identify substantial variation in protein-coding genes, including thousands of novel 5′-start sites, 3′-ends, and internal coding exons. We then determine the gene structures of over a thousand lincRNA and antisense loci. Our results open the way to direct experimental manipulation of thousands of non-coding RNAs, and demonstrate the power of ab initio reconstruction to render a comprehensive picture of mammalian transcriptomes.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 08 December 2017
                Publication date Collection: December 2017
                Volume: 18
                Issue: 12
                Electronic Location Identifier: 2659
                Affiliations
                [1 ]College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China; wangcg@ 123456hrbmu.edu.cn (C.W.); wanglz@ 123456hrbmu.edu.cn (L.W.); dingyu@ 123456hrbmu.edu.cn (Y.D.); luxy@ 123456hrbmu.edu.cn (X.L.); zhanggs@ 123456hrbmu.edu.cn (G.Z.); yangjx@ 123456hrbmu.edu.cn (J.Y.); zhenghw@ 123456hrbmu.edu.cn (H.Z.)
                [2 ]Training Center for Students Innovation and Entrepreneurship Education, Harbin Medical University, Harbin 150081, China
                Author notes
                [* ]Correspondence: wanghong84@ 123456ems.hrbmu.edu.cn (H.W.); jiangyongshuai@ 123456ems.hrbmu.edu.cn (Y.J.); xuliangde@ 123456hrbmu.edu.cn (L.X.); Tel.: +86-451-8666-9617 (L.X.)
                Article
                Publisher ID: ijms-18-02659
                DOI: 10.3390/ijms18122659
                PMC ID: 5751261
                PubMed ID: 29292750
                SO-VID: c7f21e0e-8983-455c-88aa-a19c5900dd4c
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 27 October 2017
                Date accepted : 26 November 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: lncrna structure,epigenetic regulation,rna-protein binding motif,regulation protein recruit
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: lncrna structure, epigenetic regulation, rna-protein binding motif, regulation protein recruit

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