[en] Viral tumor models have significantly contributed to our understanding of oncogenic mechanisms.
How transforming delta-retroviruses induce malignancy however remains poorly understood,
especially as viral mRNA/protein are tightly silenced in tumors. 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 non-canonical Pol IIItranscribed viral microRNAs in leukemic B-cells in the complete absence of Pol II 5’ LTR-driven
transcriptional activity. Processed from a cluster of five independent self-sufficient transcriptional
units located in a proviral region dispensable for in vivo infectivity, BLV microRNAs represent ~
40 % 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. BLV 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 in deciphering the intricate perturbations that underlie
malignant transformation.
Disciplines :
Genetics & genetic processes
Author, co-author :
Rosewick, Nicolas; Université Libre de Bruxelles (ULB) > Institut Jules Bordet > Laboratory of Experimental Hematology
