A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs.
Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA polymerase II and then processed by the Drosha endonuclease to generate approximately 60 nt pre-miRNA hairpins. Pre-miRNAs in turn are cleaved by Dicer to generate mature miRNAs. Previously, some short introns, called miRtrons, were reported to fold into pre-miRNA hairpins after splicing and debranching, and miRNAs can also be excised by Dicer cleavage of rare endogenous short hairpin RNAs. Here we report that the miRNAs encoded by murine gamma-herpesvirus 68 (MHV68) are also generated via atypical mechanisms. Specifically, MHV68 miRNAs are transcribed from RNA polymerase III promoters located within adjacent viral tRNA-like sequences. The resultant pri-miRNAs, which bear a 5' tRNA moiety, are not processed by Drosha but instead by cellular tRNase Z, which cleaves 3' to the tRNA to liberate pre-miRNA hairpins that are then processed by Dicer to yield the mature viral miRNAs.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Hal P
HP
Bogerd
Heather W
HW
Karnowski
Xuezhong
X
Cai
Jinwook
J
Shin
Michael
M
Pohlers
Bryan R
BR
Cullen
D002460:Cell Line; D004722:Endoribonucleases / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis* / Q000737:chemistry; D009690:Nucleic Acid Conformation; D034622:RNA Interference; D012320:RNA Polymerase III / Q000502:physiology; D012343:RNA, Transfer / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis* / Q000737:chemistry; D018144:Rhadinovirus / Q000235:genetics*; D043244:Ribonuclease III / Q000378:metabolism
D035683:MicroRNAs; D012367:RNA, Viral; D012343:RNA, Transfer; D012320:RNA Polymerase III; D004722:Endoribonucleases; C531011:tRNase Z, human; C517918:DROSHA protein, human; D043244:Ribonuclease III