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      Human sat III and Drosophila hsrω transcripts: a common paradigm for regulation of nuclear RNA processing in stressed cells

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      1 , 2 , * , 3 , 4
      Nucleic Acids Research
      Oxford University Press

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          Abstract

          Exposure of cells to stressful conditions elicits a highly conserved defense mechanism termed the heat shock response, resulting in the production of specialized proteins which protect the cells against the deleterious effects of stress. The heat shock response involves not only a widespread inhibition of the ongoing transcription and activation of heat shock genes, but also important changes in post-transcriptional processing. In particular, a blockade in splicing and other post-transcriptional processing has been described following stress in different organisms, together with an altered spatial distribution of the proteins involved in these activities. However, the specific mechanisms that regulate these activities under conditions of stress are little understood. Non-coding RNA molecules are increasingly known to be involved in the regulation of various activities in the cell, ranging from chromatin structure to splicing and RNA degradation. In this review, we consider two non-coding RNAs, the hsrω transcripts in Drosophila and the sat III transcripts in human cells, that seem to be involved in the dynamics of RNA-processing factors in normal and/or stressed cells, and thus provide new paradigms for understanding transcriptional and post-transcriptional regulations in normal and stressed cells.

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          Most cited references86

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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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            RNA granules

            Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationship between different classes of these granules and discuss how spatial organization regulates messenger RNA translation/decay.
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              Disruption of splicing regulated by a CUG-binding protein in myotonic dystrophy.

              Myotonic dystrophy (DM) is caused by a CTG expansion in the 3' untranslated region of the DM gene. One model of DM pathogenesis suggests that RNAs from the expanded allele create a gain-of-function mutation by the inappropriate binding of proteins to the CUG repeats. Data presented here indicate that the conserved heterogeneous nuclear ribonucleoprotein, CUG-binding protein (CUG-BP), may mediate the trans-dominant effect of the RNA. CUG-BP was found to bind to the human cardiac troponin T (cTNT) pre-messenger RNA and regulate its alternative splicing. Splicing of cTNT was disrupted in DM striated muscle and in normal cells expressing transcripts that contain CUG repeats. Altered expression of genes regulated posttranscriptionally by CUG-BP therefore may contribute to DM pathogenesis.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Research
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                November 2006
                November 2006
                04 October 2006
                : 34
                : 19
                : 5508-5514
                Affiliations
                1INSERM U309, La Tronche, F-38700, France
                2Université Joseph Fourier—Grenoble I, Institut Albert Bonniot, Domaine de la Merci F-38700, La Tronche, France
                3Department of Zoology, Banaras Hindu University Varanasi 221 005, India
                4Department of Molecular & Human Genetics, Banaras Hindu University Varanasi 221 005, India
                Author notes
                *To whom correspondence should be addressed. Tel: +33 476549470; Fax: +33 476549595; Email: caroline.jolly@ 123456ujf-grenoble.fr
                Article
                10.1093/nar/gkl711
                1636489
                17020918
                43108998-a248-47de-91fe-995ae7609a32
                © 2006 The Author(s)

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 July 2006
                : 08 September 2006
                : 11 September 2006
                Categories
                Survey and Summary

                Genetics
                Genetics

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