Article (Scientific journals)
The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
Vandermeulen, Charlotte; O'Grady, Tina; Wayet, Jérôme et al.
2021In PLoS Pathogens, 17 (9), p. 1009919
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Abstract :
[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vandermeulen, Charlotte
O'Grady, Tina
Wayet, Jérôme ;  Université de Liège - ULiège > GIGA Medical Genomics - Unit of Animal Genomics
Galvan, Bartimée  ;  Université de Liège - ULiège > GIGA Molecul. Biolog. of Diseases - Gene Expression & Cancer
Maseko, Sibusiso Bonginkhost ;  Université de Liège - ULiège > GIGA Molecul. Biolog. of Diseases - Gene Expression & Cancer
Cherkaoui, Majid
Desbuleux, Alice
Coppin, Georges
Olivet, Julien ;  Université de Liège - ULiège > GIGA
Ben Ameur, Lamya
Kataoka, Keisuke
Ogawa, Seishi
Hermine, Olivier
Marcais, Ambroise
Thiry, Marc  ;  Université de Liège - ULiège > Département des sciences de la vie > Biologie cellulaire
Mortreux, Franck
Calderwood, Michael A.
Van Weyenbergh, Johan
Peloponese, Jean-Marie
CHARLOTEAUX, Benoit ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Van den Broeke, Anne
Hill, David E.
Vidal, Marc
Dequiedt, Franck  ;  Université de Liège - ULiège > Département des sciences de la vie > Génétique et biologie moléculaires animales
Twizere, Jean-Claude  ;  Université de Liège - ULiège > Département GxABT > Microbial, food and biobased technologies
More authors (15 more) Less
Language :
English
Title :
The HTLV-1 viral oncoproteins Tax and HBZ reprogram the cellular mRNA splicing landscape.
Publication date :
2021
Journal title :
PLoS Pathogens
ISSN :
1553-7366
eISSN :
1553-7374
Publisher :
Public Library of Science, United States - California
Volume :
17
Issue :
9
Pages :
e1009919
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 December 2021

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