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      Gene regulation by long non-coding RNAs and its biological functions

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          Abstract

          Evidence accumulated over the past decade shows that long non-coding RNAs (lncRNAs) are widely expressed and have key roles in gene regulation. Recent studies have begun to unravel how the biogenesis of lncRNAs is distinct from that of mRNAs and is linked with their specific subcellular localizations and functions. Depending on their localization and their specific interactions with DNA, RNA and proteins, lncRNAs can modulate chromatin function, regulate the assembly and function of membraneless nuclear bodies, alter the stability and translation of cytoplasmic mRNAs and interfere with signalling pathways. Many of these functions ultimately affect gene expression in diverse biological and physiopathological contexts, such as in neuronal disorders, immune responses and cancer. Tissue-specific and condition-specific expression patterns suggest that lncRNAs are potential biomarkers and provide a rationale to target them clinically. In this Review, we discuss the mechanisms of lncRNA biogenesis, localization and functions in transcriptional, post-transcriptional and other modes of gene regulation, and their potential therapeutic applications.

          Abstract

          Recent studies have provided novel insight into the biogenesis of long non-coding RNAs (lncRNAs) and their specific functions. The functions of lncRNAs vary from transcriptional and post-transcriptional gene regulation to the assembly and function of membraneless nuclear bodies, and are relevant to neuronal disorders, immune responses and cancer.

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          Most cited references291

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          Targeted nucleases are powerful tools for mediating genome alteration with high precision. The RNA-guided Cas9 nuclease from the microbial clustered regularly interspaced short palindromic repeats (CRISPR) adaptive immune system can be used to facilitate efficient genome engineering in eukaryotic cells by simply specifying a 20-nt targeting sequence within its guide RNA. Here we describe a set of tools for Cas9-mediated genome editing via nonhomologous end joining (NHEJ) or homology-directed repair (HDR) in mammalian cells, as well as generation of modified cell lines for downstream functional studies. To minimize off-target cleavage, we further describe a double-nicking strategy using the Cas9 nickase mutant with paired guide RNAs. This protocol provides experimentally derived guidelines for the selection of target sites, evaluation of cleavage efficiency and analysis of off-target activity. Beginning with target design, gene modifications can be achieved within as little as 1-2 weeks, and modified clonal cell lines can be derived within 2-3 weeks.
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            A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language?

            Here, we present a unifying hypothesis about how messenger RNAs, transcribed pseudogenes, and long noncoding RNAs "talk" to each other using microRNA response elements (MREs) as letters of a new language. We propose that this "competing endogenous RNA" (ceRNA) activity forms a large-scale regulatory network across the transcriptome, greatly expanding the functional genetic information in the human genome and playing important roles in pathological conditions, such as cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                linglingchen@sibcb.ac.cn
                maitehuarte@unav.es
                Journal
                Nat Rev Mol Cell Biol
                Nat Rev Mol Cell Biol
                Nature Reviews. Molecular Cell Biology
                Nature Publishing Group UK (London )
                1471-0072
                1471-0080
                22 December 2020
                : 1-23
                Affiliations
                [1 ]GRID grid.5924.a, ISNI 0000000419370271, Center for Applied Medical Research, University of Navarra, ; Pamplona, Spain
                [2 ]Institute of Health Research of Navarra (IdiSNA), Pamplona, Spain
                [3 ]GRID grid.507739.f, ISNI 0000 0001 0061 254X, State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, ; Shanghai, China
                [4 ]GRID grid.440637.2, ISNI 0000 0004 4657 8879, School of Life Science and Technology, ShanghaiTech University, ; Shanghai, China
                [5 ]GRID grid.410726.6, ISNI 0000 0004 1797 8419, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, ; Hangzhou, China
                Author information
                http://orcid.org/0000-0001-8261-4214
                http://orcid.org/0000-0001-9501-0305
                http://orcid.org/0000-0003-3753-6493
                Article
                315
                10.1038/s41580-020-00315-9
                7754182
                33353982
                23a0e92b-8676-4049-bad4-1cea10aa61a5
                © Springer Nature Limited 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 5 November 2020
                Categories
                Review Article

                long non-coding rnas,transcription
                long non-coding rnas, transcription

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