A Mammalian Herpesvirus Uses Noncanonical Expression and Processing Mechanisms to Generate Viral MicroRNAs

被引:159
作者
Bogerd, Hal P. [1 ,2 ]
Karnowski, Heather W. [1 ,2 ]
Cai, Xuezhong [1 ,2 ]
Shin, Jinwook [1 ,2 ]
Pohlers, Michael [1 ,2 ]
Cullen, Bryan R. [1 ,2 ]
机构
[1] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA
[2] Duke Univ, Med Ctr, Ctr Virol, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
RNA-POLYMERASE-III; MESSENGER-RNAS; TRNASE-Z; DROSHA; CELLS; RECOGNITION; GENES; IDENTIFICATION; TRANSCRIPTS; PRECURSORS;
D O I
10.1016/j.molcel.2009.12.016
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA polymerase II and then processed by the Drosha endonuclease to generate similar to 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.
引用
收藏
页码:135 / 142
页数:8
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