Bovine Leukemia Virus Small Noncoding RNAs Are Functional Elements That Regulate Replication and Contribute to Oncogenesis In Vivo.
Retroviruses are not expected to encode miRNAs because of the potential problem of self-cleavage of their genomic RNAs. This assumption has recently been challenged by experiments showing that bovine leukemia virus (BLV) encodes miRNAs from intragenomic Pol III promoters. The BLV miRNAs are abundantly expressed in B-cell tumors in the absence of significant levels of genomic and subgenomic viral RNAs. Using deep RNA sequencing and functional reporter assays, we show that miRNAs mediate the expression of genes involved in cell signaling, cancer and immunity. We further demonstrate that BLV miRNAs are essential to induce B-cell tumors in an experimental model and to promote efficient viral replication in the natural host.
Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Liège, Belgium.|Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
Nicolas A
0000-0002-9410-8738
NA
Gillet
Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Liège, Belgium.|Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
Malik
M
Hamaidia
Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Liège, Belgium.|Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
Alix
A
de Brogniez
Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Castelar, Argentina.
Gerónimo
G
Gutiérrez
Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Liège, Belgium.|Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
Nathalie
N
Renotte
National Veterinary Research Institute, Pulawy, Poland.
Michal
M
Reichert
Instituto de Virología, Centro de Investigaciones en Ciencias Veterinarias y Agronómicas, Castelar, Argentina.
Karina
K
Trono
Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA), University of Liège, Liège, Belgium.|Molecular and Cellular Biology, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium.
Luc
L
Willems
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002417:Cattle; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016583:Enzootic Bovine Leukosis; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D001909:Leukemia Virus, Bovine / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics; D012756:Sheep; D014779:Virus Replication / Q000235:genetics*
D035683:MicroRNAs; D012367:RNA, Viral