The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcrip...

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Autores principales:	Charlotte Vandermeulen, Tina O'Grady, Jerome Wayet, Bartimee Galvan, Sibusiso Maseko, Majid Cherkaoui, Alice Desbuleux, Georges Coppin, Julien Olivet, Lamya Ben Ameur, Keisuke Kataoka, Seishi Ogawa, Olivier Hermine, Ambroise Marcais, Marc Thiry, Franck Mortreux, Michael A Calderwood, Johan Van Weyenbergh, Jean-Marie Peloponese, Benoit Charloteaux, Anne Van den Broeke, David E Hill, Marc Vidal, Franck Dequiedt, Jean-Claude Twizere
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/768541b3f7ce458ea9bab656e35d5479
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spelling	oai:doaj.org-article:768541b3f7ce458ea9bab656e35d54792021-12-02T20:00:09ZThe HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.1553-73661553-737410.1371/journal.ppat.1009919https://doaj.org/article/768541b3f7ce458ea9bab656e35d54792021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009919https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome.Charlotte VandermeulenTina O'GradyJerome WayetBartimee GalvanSibusiso MasekoMajid CherkaouiAlice DesbuleuxGeorges CoppinJulien OlivetLamya Ben AmeurKeisuke KataokaSeishi OgawaOlivier HermineAmbroise MarcaisMarc ThiryFranck MortreuxMichael A CalderwoodJohan Van WeyenberghJean-Marie PeloponeseBenoit CharloteauxAnne Van den BroekeDavid E HillMarc VidalFranck DequiedtJean-Claude TwizerePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009919 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Charlotte Vandermeulen Tina O'Grady Jerome Wayet Bartimee Galvan Sibusiso Maseko Majid Cherkaoui Alice Desbuleux Georges Coppin Julien Olivet Lamya Ben Ameur Keisuke Kataoka Seishi Ogawa Olivier Hermine Ambroise Marcais Marc Thiry Franck Mortreux Michael A Calderwood Johan Van Weyenbergh Jean-Marie Peloponese Benoit Charloteaux Anne Van den Broeke David E Hill Marc Vidal Franck Dequiedt Jean-Claude Twizere The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
description	Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome.
format	article
author	Charlotte Vandermeulen Tina O'Grady Jerome Wayet Bartimee Galvan Sibusiso Maseko Majid Cherkaoui Alice Desbuleux Georges Coppin Julien Olivet Lamya Ben Ameur Keisuke Kataoka Seishi Ogawa Olivier Hermine Ambroise Marcais Marc Thiry Franck Mortreux Michael A Calderwood Johan Van Weyenbergh Jean-Marie Peloponese Benoit Charloteaux Anne Van den Broeke David E Hill Marc Vidal Franck Dequiedt Jean-Claude Twizere
author_facet	Charlotte Vandermeulen Tina O'Grady Jerome Wayet Bartimee Galvan Sibusiso Maseko Majid Cherkaoui Alice Desbuleux Georges Coppin Julien Olivet Lamya Ben Ameur Keisuke Kataoka Seishi Ogawa Olivier Hermine Ambroise Marcais Marc Thiry Franck Mortreux Michael A Calderwood Johan Van Weyenbergh Jean-Marie Peloponese Benoit Charloteaux Anne Van den Broeke David E Hill Marc Vidal Franck Dequiedt Jean-Claude Twizere
author_sort	Charlotte Vandermeulen
title	The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
title_short	The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
title_full	The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
title_fullStr	The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
title_full_unstemmed	The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
title_sort	htlv-1 viral oncoproteins tax and hbz reprogram the cellular mrna splicing landscape.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/768541b3f7ce458ea9bab656e35d5479
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The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.

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