TY - JOUR
T1 - The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape
AU - Vandermeulen, Charlotte
AU - O’Grady, Tina
AU - Wayet, Jerome
AU - Galvan, Bartimee
AU - Maseko, Sibusiso
AU - Cherkaoui, Majid
AU - Desbuleux, Alice
AU - Coppin, Georges
AU - Olivet, Julien
AU - Ameur, Lamya Ben
AU - Kataoka, Keisuke
AU - Ogawa, Seishi
AU - Hermine, Olivier
AU - Marcais, Ambroise
AU - Thiry, Marc
AU - Mortreux, Franck
AU - Calderwood, Michael A.
AU - van Weyenbergh, Johan
AU - Peloponese, Jean Marie
AU - Charloteaux, Benoit
AU - van den Broeke, Anne
AU - Hill, David E.
AU - Vidal, Marc
AU - Dequiedt, Franck
AU - Twizere, Jean Claude
N1 - Publisher Copyright:
© 2021 Vandermeulen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.ppat.1009919
DO - 10.1371/journal.ppat.1009919
M3 - Article
C2 - 34543356
AN - SCOPUS:85115356925
SN - 1553-7366
VL - 17
JO - PLoS Pathogens
JF - PLoS Pathogens
IS - 9
M1 - e1009919
ER -
