Article (Scientific journals)
Deep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma
Rosewick, Nicolas; Momont, Mélanie; Durkin, Keith et al.
2013In Proceedings of the National Academy of Sciences of the United States of America
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Keywords :
non-coding RNA; oncogenesis; retrovirus silencing
Abstract :
[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
Momont, Mélanie ;  Université de Liège - ULiège > GIGA - Membres
Durkin, Keith  ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Takeda, Haruko ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Caiment, Florian
Cleuter, Yvette
Vernin, Céline
Mortreux, Franck
Wattel, Eric
Burny, Arsène ;  Université de Liège - ULiège > Agro Biotech Gembloux
Georges, Michel  ;  Université de Liège - ULiège > Département de productions animales > GIGA-R : Génomique animale
Van den Broeke, Anne;  Université Libre de Bruxelles (ULB) > Institut Jules Bordet > Laboratory of Experimental Hematology
Language :
English
Title :
Deep sequencing reveals abundant non-canonical retroviral microRNAs in B-cell leukemia/lymphoma
Publication date :
23 January 2013
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 11 January 2013

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