A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs.
A mammalian herpesvirus uses noncanonical expression and processing mechanisms to generate viral MicroRNAs.
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DOI：
10.1016/j.molcel.2009.12.016
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发表时间：
2010-01-15
期刊：
影响因子：
16
通讯作者：
Cullen BR
中科院分区：
文献类型：
--
作者：
Bogerd HP;Karnowski HW;Cai X;Shin J;Pohlers M;Cullen BR
规范的初级微小RNA(Pri-miRNA)前体由RNA聚合酶II转录，然后被DROSHA内切酶处理产生∼60nt的前miRNA发夹。前miRNAs又被Diller切割成成熟的miRNAs。以前，有报道称一些被称为miRtron的短内含子在剪接和去分支后折叠成前miRNA发夹，并且miRNAs也可以通过切割稀有的内源性短发夹RNA而被切除。在这里，我们报告了由小鼠γ疱疹病毒68(MHV68)编码的miRNAs也是通过非典型机制产生的。具体地说，MHV68 miRNAs是从位于相邻病毒tRNA样序列中的RNA聚合酶III启动子转录而来的。产生的pri-miRNAs带有5‘tRNA部分，不是由DROSHA处理，而是由细胞tRNase Z处理，它将3’裂解到tRNA上，释放出前miRNA发夹，然后由DICER处理，产生成熟的病毒miRNAs。
Canonical primary microRNA (pri-miRNA) precursors are transcribed by RNA polymerase II and then processed by the Drosha endonuclease to generate ∼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 γ-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 a 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.
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