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Here, using deep sequencing of broad windows of small RNA sizes in the bovine leukemia virus ovine model of leukemia\/lymphoma, we provide in vivo evidence of the production of noncanonical RNA polymerase III (Pol III)-transcribed viral microRNAs in leukemic B cells in the complete absence of Pol II 5\u2032-LTR\u2013driven transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional units located in a proviral region dispensable for in vivo infectivity, bovine leukemia virus microRNAs represent \u223c40% of all microRNAs in both experimental and natural malignancy. They are subject to strong purifying selection and associate with Argonautes, consistent with a critical function in silencing of important cellular and\/or viral targets. Bovine leukemia virus microRNAs are strongly expressed in preleukemic and malignant cells in which structural and regulatory gene expression is repressed, suggesting a key role in tumor onset and progression. Understanding how Pol III-dependent microRNAs subvert cellular and viral pathways will contribute to deciphering the intricate perturbations that underlie malignant transformation.<\/jats:p>","DOI":"10.1073\/pnas.1213842110","type":"journal-article","created":{"date-parts":[[2013,1,24]],"date-time":"2013-01-24T05:03:36Z","timestamp":1359003816000},"page":"2306-2311","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia\/lymphoma"],"prefix":"10.1073","volume":"110","author":[{"given":"Nicolas","family":"Rosewick","sequence":"first","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"},{"name":"Laboratory of Experimental Hematology, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Momont","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Durkin","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruko","family":"Takeda","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Caiment","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvette","family":"Cleuter","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Vernin","sequence":"additional","affiliation":[{"name":"Oncovirologie et Bioth\u00e9rapies, Unit\u00e9 Mixte de Recherche 5239, Ecole Normale Sup\u00e9rieure Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Mortreux","sequence":"additional","affiliation":[{"name":"Oncovirologie et Bioth\u00e9rapies, Unit\u00e9 Mixte de Recherche 5239, Ecole Normale Sup\u00e9rieure Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wattel","sequence":"additional","affiliation":[{"name":"Oncovirologie et Bioth\u00e9rapies, Unit\u00e9 Mixte de Recherche 5239, Ecole Normale Sup\u00e9rieure Lyon, 69008 Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ars\u00e8ne","family":"Burny","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Hematology, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Georges","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Van den Broeke","sequence":"additional","affiliation":[{"name":"Unit of Animal Genomics, Groupe Interdisciplinaire G\u00e9noprot\u00e9omique Appliqu\u00e9e, Universit\u00e9 de Li\u00e8ge, 4000 Li\u00e8ge, Belgium;"},{"name":"Laboratory of Experimental Hematology, Institut Jules Bordet, Universit\u00e9 Libre de Bruxelles, 1000 Brussels, Belgium; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,1,23]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"313","volume-title":"Viruses and Cancer","author":"Burny A","year":"1994","unstructured":"A Burny, et al., Bovine Leukemia Virus: Biology and mode of transformation. 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