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      RNA and Proteins: Mutual Respect

      review-article
      a , 1
      F1000Research
      F1000Research
      Ribonucleoprotein Particles, RNPs, RNA-protein interaction, Xist, lncRNA, U4/5/6 tri-snRNP complex

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          Abstract

          Proteins and RNA are often found in ribonucleoprotein particles (RNPs), where they function in cellular processes to synthesize proteins (the ribosome), chemically modify RNAs (small nucleolar RNPs), splice pre-mRNAs (the spliceosome), and, on a larger scale, sequester RNAs, degrade them, or process them (P bodies, Cajal bodies, and nucleoli). Each RNA–protein interaction is a story in itself, as both molecules can change conformation, compete for binding sites, and regulate cellular functions. Recent studies of Xist long non-coding RNP, the U4/5/6 tri-small nuclear RNP complex, and an activated state of a spliceosome reveal new features of RNA interactions with proteins, and, although their stories are incomplete, they are already fascinating.

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          Most cited references72

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          The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome.

          Many large noncoding RNAs (lncRNAs) regulate chromatin, but the mechanisms by which they localize to genomic targets remain unexplored. We investigated the localization mechanisms of the Xist lncRNA during X-chromosome inactivation (XCI), a paradigm of lncRNA-mediated chromatin regulation. During the maintenance of XCI, Xist binds broadly across the X chromosome. During initiation of XCI, Xist initially transfers to distal regions across the X chromosome that are not defined by specific sequences. Instead, Xist identifies these regions by exploiting the three-dimensional conformation of the X chromosome. Xist requires its silencing domain to spread across actively transcribed regions and thereby access the entire chromosome. These findings suggest a model in which Xist coats the X chromosome by searching in three dimensions, modifying chromosome structure, and spreading to newly accessible locations.
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            Histone core modifications regulating nucleosome structure and dynamics.

            Post-translational modifications of histones regulate all DNA-templated processes, including replication, transcription and repair. These modifications function as platforms for the recruitment of specific effector proteins, such as transcriptional regulators or chromatin remodellers. Recent data suggest that histone modifications also have a direct effect on nucleosomal architecture. Acetylation, methylation, phosphorylation and citrullination of the histone core may influence chromatin structure by affecting histone-histone and histone-DNA interactions, as well as the binding of histones to chaperones.
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              Evolution of SR protein and hnRNP splicing regulatory factors.

              The splicing of pre-mRNAs is an essential step of gene expression in eukaryotes. Introns are removed from split genes through the activities of the spliceosome, a large ribonuclear machine that is conserved throughout the eukaryotic lineage. While unicellular eukaryotes are characterized by less complex splicing, pre-mRNA splicing of multicellular organisms is often associated with extensive alternative splicing that significantly enriches their proteome. The alternative selection of splice sites and exons permits multicellular organisms to modulate gene expression patterns in a cell type-specific fashion, thus contributing to their functional diversification. Alternative splicing is a regulated process that is mainly influenced by the activities of splicing regulators, such as SR proteins or hnRNPs. These modular factors have evolved from a common ancestor through gene duplication events to a diverse group of splicing regulators that mediate exon recognition through their sequence-specific binding to pre-mRNAs. Given the strong correlations between intron expansion, the complexity of pre-mRNA splicing, and the emergence of splicing regulators, it is argued that the increased presence of SR and hnRNP proteins promoted the evolution of alternative splicing through relaxation of the sequence requirements of splice junctions. Copyright © 2011 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000Research (London, UK )
                2046-1402
                27 March 2017
                2017
                : 6
                : 345
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO, 63110, USA
                Author notes

                Competing interests: The author declares that she has no competing interests.

                Author information
                http://orcid.org/0000-0003-2276-0310
                Article
                10.12688/f1000research.10572.1
                5373437
                f56d6feb-f7d4-4ad6-9a6e-ce34a3de87f4
                Copyright: © 2017 Hall KB

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 March 2017
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles
                Biomacromolecule-Ligand Interactions
                Control of Gene Expression
                Macromolecular Assemblies & Machines
                Nuclear Structure & Function
                Protein Chemistry & Proteomics
                Structure: RNA

                ribonucleoprotein particles,rnps,rna-protein interaction,xist,lncrna,u4/5/6 tri-snrnp complex

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