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Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region

Herpesvirus saimiri, an oncogenic herpesvirus, during latency produces seven small nuclear RNAs, called the Herpesvirus saimiri U RNAs (HSUR1–7). HSUR1 mediates degradation of the host microRNA, miR-27, via a process that requires imperfect base-pairing. The decreased levels of miR-27 lead to prolon...

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Detalles Bibliográficos
Autores principales: Pawlica, Paulina, Moss, Walter N., Steitz, Joan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931111/
https://www.ncbi.nlm.nih.gov/pubmed/27335146
http://dx.doi.org/10.1261/rna.054817.115
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author Pawlica, Paulina
Moss, Walter N.
Steitz, Joan A.
author_facet Pawlica, Paulina
Moss, Walter N.
Steitz, Joan A.
author_sort Pawlica, Paulina
collection PubMed
description Herpesvirus saimiri, an oncogenic herpesvirus, during latency produces seven small nuclear RNAs, called the Herpesvirus saimiri U RNAs (HSUR1–7). HSUR1 mediates degradation of the host microRNA, miR-27, via a process that requires imperfect base-pairing. The decreased levels of miR-27 lead to prolonged T-cell activation and likely contribute to oncogenesis. To gain insight into HSUR1-mediated degradation of miR-27, we probed the in vivo secondary structure of HSUR1 and coupled this with bioinformatic structural analyses. The results suggest that HSUR1 adopts a conformation different than previously believed and that the region complementary to miR-27 lacks stable structure. To determine whether HSUR1 structural flexibility is important for its ability to mediate miR-27 degradation, we performed structurally informative mutagenic analyses of HSUR1. HSUR1 mutants in which the miR-27 binding site sequence is preserved, but sequestered in predicted helices, lose their ability to decrease miR-27 levels. These results indicate that the HSUR1 miR27-binding region must be available in a conformationally flexible segment for noncoding RNA function.
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spelling pubmed-49311112017-08-01 Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region Pawlica, Paulina Moss, Walter N. Steitz, Joan A. RNA Report Herpesvirus saimiri, an oncogenic herpesvirus, during latency produces seven small nuclear RNAs, called the Herpesvirus saimiri U RNAs (HSUR1–7). HSUR1 mediates degradation of the host microRNA, miR-27, via a process that requires imperfect base-pairing. The decreased levels of miR-27 lead to prolonged T-cell activation and likely contribute to oncogenesis. To gain insight into HSUR1-mediated degradation of miR-27, we probed the in vivo secondary structure of HSUR1 and coupled this with bioinformatic structural analyses. The results suggest that HSUR1 adopts a conformation different than previously believed and that the region complementary to miR-27 lacks stable structure. To determine whether HSUR1 structural flexibility is important for its ability to mediate miR-27 degradation, we performed structurally informative mutagenic analyses of HSUR1. HSUR1 mutants in which the miR-27 binding site sequence is preserved, but sequestered in predicted helices, lose their ability to decrease miR-27 levels. These results indicate that the HSUR1 miR27-binding region must be available in a conformationally flexible segment for noncoding RNA function. Cold Spring Harbor Laboratory Press 2016-08 /pmc/articles/PMC4931111/ /pubmed/27335146 http://dx.doi.org/10.1261/rna.054817.115 Text en © 2016 Pawlica et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Report
Pawlica, Paulina
Moss, Walter N.
Steitz, Joan A.
Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title_full Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title_fullStr Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title_full_unstemmed Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title_short Host miRNA degradation by Herpesvirus saimiri small nuclear RNA requires an unstructured interacting region
title_sort host mirna degradation by herpesvirus saimiri small nuclear rna requires an unstructured interacting region
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4931111/
https://www.ncbi.nlm.nih.gov/pubmed/27335146
http://dx.doi.org/10.1261/rna.054817.115
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