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      Is Open Access

      DUSP11 – An RNA phosphatase that regulates host and viral non-coding RNAs in mammalian cells

      review-article
      ,
      RNA Biology
      Taylor & Francis
      Argonaute, BLV, dicer, DUSP11, miRNA, miRNA biogenesis, PIR-1, RNAi, triphosphate, VA RNA

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          ABSTRACT

          Dual-specificity phosphatase 11 (DUSP11) is a conserved protein tyrosine phosphatase (PTP) in metazoans. The cellular substrates and physiologic activities of DUSP11 remain largely unknown. In nematodes, DUSP11 is required for normal development and RNA interference against endogenous RNAs (endo-RNAi) via molecular mechanisms that are not well understood. However, mammals lack analogous endo-RNAi pathways and consequently, a role for DUSP11 in mammalian RNA silencing was unanticipated. Recent work from our laboratory demonstrated that DUSP11 activity alters the silencing potential of noncanonical viral miRNAs in mammalian cells. Our studies further uncovered direct cellular substrates of DUSP11 and suggest that DUSP11 is part of regulatory pathway that controls the abundance of select triphosphorylated noncoding RNAs. Here, we highlight recent findings and present new data that advance understanding of mammalian DUSP11 during gene silencing and discuss the emerging biological activities of DUSP11 in mammalian cells.

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          Most cited references58

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          Origins and Mechanisms of miRNAs and siRNAs.

          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            MicroRNA biogenesis: coordinated cropping and dicing.

            V Kim (2005)
            The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, approximately 22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
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              RIG-I-mediated antiviral responses to single-stranded RNA bearing 5'-phosphates.

              Double-stranded RNA (dsRNA) produced during viral replication is believed to be the critical trigger for activation of antiviral immunity mediated by the RNA helicase enzymes retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). We showed that influenza A virus infection does not generate dsRNA and that RIG-I is activated by viral genomic single-stranded RNA (ssRNA) bearing 5'-phosphates. This is blocked by the influenza protein nonstructured protein 1 (NS1), which is found in a complex with RIG-I in infected cells. These results identify RIG-I as a ssRNA sensor and potential target of viral immune evasion and suggest that its ability to sense 5'-phosphorylated RNA evolved in the innate immune system as a means of discriminating between self and nonself.
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                Author and article information

                Journal
                RNA Biol
                RNA Biol
                KRNB
                krnb20
                RNA Biology
                Taylor & Francis
                1547-6286
                1555-8584
                2017
                17 April 2017
                17 April 2017
                : 14
                : 11
                : 1457-1465
                Affiliations
                The University of Texas at Austin, Center for Systems and Synthetic Biology, Center for Infectious Disease and Department of Molecular Biosciences , Austin, TX, USA
                Author notes
                CONTACT Christopher S. Sullivan Chris_sullivan@ 123456austin.utexas.edu ; chris_sullivan@ 123456mail.utexas.edu , Infectious Disease and Department of Molecular Biosciences, University of Texas , Austin, 1 University Station A5000, Austin, Texas, 78712–0162, USA

                 

                Article
                1306169
                10.1080/15476286.2017.1306169
                5785229
                28296624
                3b4735d9-f7c7-4be0-9058-d7440e38c364
                © 2017 The Author(s). Published with license by Taylor & Francis Group, LLC

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

                History
                : 16 February 2017
                : 1 March 2017
                : 9 March 2017
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 84, Pages: 9
                Categories
                Point Of View

                Molecular biology
                argonaute,blv,dicer,dusp11,mirna,mirna biogenesis,pir-1,rnai,triphosphate,va rna
                Molecular biology
                argonaute, blv, dicer, dusp11, mirna, mirna biogenesis, pir-1, rnai, triphosphate, va rna

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