title: Characterization of new RNA polymerase III and RNA polymerase II transcriptional promoters in the Bovine Leukemia Virus genome.
abstract: Bovine leukemia virus latency is a viral strategy used to escape from the host immune system and contribute to tumor development. However, a highly expressed BLV micro-RNA cluster has been reported, suggesting that the BLV silencing is not complete. Here, we demonstrate the in vivo recruitment of RNA polymerase III to the BLV miRNA cluster both in BLV-latently infected cell lines and in ovine BLV-infected primary cells, through a canonical type 2 RNAPIII promoter. Moreover, by RPC6-knockdown, we showed a direct functional link between RNAPIII transcription and BLV miRNAs expression. Furthermore, both the tumor- and the quiescent-related isoforms of RPC7 subunits were recruited to the miRNA cluster. We showed that the BLV miRNA cluster was enriched in positive epigenetic marks. Interestingly, we demonstrated the in vivo recruitment of RNAPII at the 3'LTR/host genomic junction, associated with positive epigenetic marks. Functionally, we showed that the BLV LTR exhibited a strong antisense promoter activity and identified cis-acting elements of an RNAPII-dependent promoter. Finally, we provided evidence for an in vivo collision between RNAPIII and RNAPII convergent transcriptions. Our results provide new insights into alternative ways used by BLV to counteract silencing of the viral 5'LTR promoter.
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Van Driessche
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodari
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Nadège
authors.initials: N
authors.lastname: Delacourt
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Fauquenoy
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Vanhulle
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Arsène
authors.initials: A
authors.lastname: Burny
authors.affiliation: Institut Universitaire de Technologie Louis Pasteur de Schiltigheim, University of Strasbourg, Schiltigheim, F-67300, France.|Institut de Parasitologie et de Pathologie Tropicale, Laboratory of Dynamic of Host-Pathogen Interactions (DHPI), EA7292, University of Strasbourg, Strasbourg, F-67000, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Rohr
authors.affiliation: Service of Molecular Virology, Department of Molecular Biology (DBM), Université Libre de Bruxelles (ULB), Gosselies, B-6041, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D002460:Cell Line; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D016679:Genome, Viral; D057809:HEK293 Cells; D006801:Humans; D001909:Leukemia Virus, Bovine / Q000201:enzymology* / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D021122:Protein Subunits; D012319:RNA Polymerase II / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012320:RNA Polymerase III / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012756:Sheep; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D021122:Protein Subunits; D034741:RNA, Small Interfering; D012319:RNA Polymerase II; D012320:RNA Polymerase III