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      Splicing regulation by long noncoding RNAs

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          Abstract

          Massive high-throughput sequencing techniques allowed the identification of thousands of noncoding RNAs (ncRNAs) and a plethora of different mRNA processing events occurring in higher organisms. Long ncRNAs can act directly as long transcripts or can be processed into active small si/miRNAs. They can modulate mRNA cleavage, translational repression or the epigenetic landscape of their target genes. Recently, certain long ncRNAs have been shown to play a crucial role in the regulation of alternative splicing in response to several stimuli or during disease. In this review, we focus on recent discoveries linking gene regulation by alternative splicing and its modulation by long and small ncRNAs.

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          Most cited references104

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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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            The multifunctional nucleolus.

            The nucleolus is a distinct subnuclear compartment that was first observed more than 200 years ago. Nucleoli assemble around the tandemly repeated ribosomal DNA gene clusters and 28S, 18S and 5.8S ribosomal RNAs (rRNAs) are transcribed as a single precursor, which is processed and assembled with the 5S rRNA into ribosome subunits. Although the nucleolus is primarily associated with ribosome biogenesis, several lines of evidence now show that it has additional functions. Some of these functions, such as regulation of mitosis, cell-cycle progression and proliferation, many forms of stress response and biogenesis of multiple ribonucleoprotein particles, will be discussed, as will the relation of the nucleolus to human diseases.
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              Understanding alternative splicing: towards a cellular code.

              In violation of the 'one gene, one polypeptide' rule, alternative splicing allows individual genes to produce multiple protein isoforms - thereby playing a central part in generating complex proteomes. Alternative splicing also has a largely hidden function in quantitative gene control, by targeting RNAs for nonsense-mediated decay. Traditional gene-by-gene investigations of alternative splicing mechanisms are now being complemented by global approaches. These promise to reveal details of the nature and operation of cellular codes that are constituted by combinations of regulatory elements in pre-mRNA substrates and by cellular complements of splicing regulators, which together determine regulated splicing pathways.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                16 March 2018
                7 February 2018
                7 February 2018
                : 46
                : 5
                : 2169-2184
                Affiliations
                [1 ]Institute of Plant Sciences Paris-Saclay (IPS2), CNRS, INRA, Universities Paris-Sud, Evry and Paris-Diderot, Sorbonne Paris-Cite, University of Paris-Saclay, Batiment 630, 91405 Orsay, France
                [2 ]Instituto de Agrobiotecnología del Litoral, CONICET, Universidad Nacional del Litoral, Colectora Ruta Nacional 168 km 0, 3000 Santa Fe, Argentina
                Author notes
                To whom correspondence should be addressed. Tel: +33 1 69153304; Fax: +33 1 69153304; Email: martin.crespi@ 123456ips2.universite-paris-saclay.fr . Correspondence may also be addressed to Federico Ariel. Email: fariel@ 123456santafe-conicet.gov.ar
                Author information
                http://orcid.org/0000-0001-8478-8808
                Article
                gky095
                10.1093/nar/gky095
                5861421
                29425321
                74d3bf69-24be-40ba-a0f4-8d62e36edfab
                © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 01 February 2018
                : 05 January 2018
                : 10 October 2017
                Page count
                Pages: 16
                Categories
                Survey and Summary

                Genetics
                Genetics

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