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

• DOI: 10.1371/journal.ppat.1009919
• Publication Date: 2021-09-20T18:31:58Z
• Authors: Charlotte Vanderm...; 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. Calder...; Johan Van Weyenbergh; Jean-Marie Pelopo...; Benoit Charloteaux; Anne Van den Broeke; David E. Hill; Marc Vidal; Franck Dequiedt; Jean-Claude Twizere
• Keywords: Interactome; Transcription; Spliceosome

Viral infections are known to hijack the transcription and translation of host cell. However, extent which viral proteins coordinate these perturbations remains unclear. Here we used a model system, human T-cell leukemia virus type 1 (HTLV-1), systematically analyzed transcriptome interactome key effectors oncoviral Tax HBZ. We showed that HBZ target distinct but also common factors. Unexpectedly, uncovered large set interactions with RNA-binding proteins, including U2 auxiliary factor subunit (U2AF2), cellular regulator pre-mRNA splicing. discovered perturb splicing landscape by altering cassette exons in opposing manners, inducing exon inclusion while induces exclusion. Among Tax- HBZ-dependent changes, identify events altered Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, well-known cancer census genes. Our mapping approach, applicable other oncogenes, has identified spliceosome perturbation as novel mechanism coordinated reprogram transcriptome.