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      Functional diversity of small nucleolar RNAs

      research-article
      1 , 2 , 3 , 1 , 2 , 3 , 4
      Nucleic Acids Research
      Oxford University Press

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          Abstract

          Small nucleolar RNAs (snoRNAs) are short non-protein-coding RNAs with a long-recognized role in tuning ribosomal and spliceosomal function by guiding ribose methylation and pseudouridylation at targeted nucleotide residues of ribosomal and small nuclear RNAs, respectively. SnoRNAs are increasingly being implicated in regulation of new types of post-transcriptional processes, for example rRNA acetylation, modulation of splicing patterns, control of mRNA abundance and translational efficiency, or they themselves are processed to shorter stable RNA species that seem to be the principal or alternative bioactive isoform. Intriguingly, some display unusual cellular localization under exogenous stimuli, or tissue-specific distribution. Here, we discuss the new and unforeseen roles attributed to snoRNAs, focusing on the presumed mechanisms of action. Furthermore, we review the experimental approaches to study snoRNA function, including high resolution RNA:protein and RNA:RNA interaction mapping, techniques for analyzing modifications on targeted RNAs, and cellular and animal models used in snoRNA biology research.

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          Most cited references164

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          HITS-CLIP yields genome-wide insights into brain alternative RNA processing

          Summary Protein-RNA interactions play critical roles in all aspects of gene expression. Here we develop a genome-wide means of mapping protein-RNA binding sites in vivo, by high throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP). HITS-CLIP analysis of the neuron-specific splicing factor Nova2 revealed extremely reproducible RNA binding maps in multiple mouse brains. These maps provide genome-wide in vivo biochemical footprints confirming the previous prediction that the position of Nova binding determines the outcome of alternative splicing; moreover, they are sufficiently powerful to predict Nova action de novo. HITS-CLIP revealed a large number of Nova-RNA interactions in 3′ UTRs, leading to the discovery that Nova regulates alternative polyadenylation in the brain. HITS-CLIP, therefore, provides a robust, unbiased means to identify functional protein-RNA interactions in vivo.
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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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              Transcriptome-wide mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA and mRNA.

              Pseudouridine is the most abundant RNA modification, yet except for a few well-studied cases, little is known about the modified positions and their function(s). Here, we develop Ψ-seq for transcriptome-wide quantitative mapping of pseudouridine. We validate Ψ-seq with spike-ins and de novo identification of previously reported positions and discover hundreds of unique sites in human and yeast mRNAs and snoRNAs. Perturbing pseudouridine synthases (PUS) uncovers which pseudouridine synthase modifies each site and their target sequence features. mRNA pseudouridinylation depends on both site-specific and snoRNA-guided pseudouridine synthases. Upon heat shock in yeast, Pus7p-mediated pseudouridylation is induced at >200 sites, and PUS7 deletion decreases the levels of otherwise pseudouridylated mRNA, suggesting a role in enhancing transcript stability. rRNA pseudouridine stoichiometries are conserved but reduced in cells from dyskeratosis congenita patients, where the PUS DKC1 is mutated. Our work identifies an enhanced, transcriptome-wide scope for pseudouridine and methods to dissect its underlying mechanisms and function. Copyright © 2014 Elsevier Inc. All rights reserved.
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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
                28 February 2020
                12 December 2019
                12 December 2019
                : 48
                : 4
                : 1627-1651
                Affiliations
                [1 ] University of Ljubljana, Faculty of Pharmacy , Aškerčeva cesta 7, SI1000 Ljubljana, Slovenia
                [2 ] Jozef Stefan Institute, Department of Biotechnology , Jamova cesta 39, SI1000 Ljubljana, Slovenia
                [3 ] Biomedical Research Institute BRIS , Puhova ulica 10, SI1000 Ljubljana, Slovenia
                [4 ] University of Ljubljana, Faculty of Chemistry and Chemical Technology , Večna pot 113, SI1000 Ljubljana, Slovenia
                Author notes
                To whom correspondence should be addressed. Tel: +386 1 4769 570, Fax: +386 1 4258 031; Email: tomaz.bratkovic@ 123456ffa.uni-lj.si
                Correspondence may also be addressed to Boris Rogelj. Tel: +386 1 4773 611; Fax: +386 1 4773 594; Email: boris.rogelj@ 123456ijs.si
                Author information
                http://orcid.org/0000-0001-8367-5465
                http://orcid.org/0000-0003-3898-1943
                Article
                gkz1140
                10.1093/nar/gkz1140
                7038934
                31828325
                eed24259-93f4-4249-8eea-2e91232c7594
                © The Author(s) 2019. 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 Non-Commercial 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
                : 05 December 2019
                : 17 November 2019
                : 04 October 2019
                Page count
                Pages: 25
                Funding
                Funded by: Slovenian Research Agency 10.13039/501100004329
                Award ID: P4-0127
                Award ID: J3-9263
                Funded by: Foundation for Prader-Willi Research 10.13039/100002889
                Funded by: Javna Agencija za Raziskovalno Dejavnost RS 10.13039/501100004329
                Categories
                Survey and Summary

                Genetics
                Genetics

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