Haussecker Dirk, Cao Dan, Huang Yong, Parameswaran Poornima, Fire Andrew Z, Kay Mark A
Department of Pediatrics, Stanford University, 300 Pasteur Dr., Stanford, California 94305, USA.
Nat Struct Mol Biol. 2008 Jul;15(7):714-21. doi: 10.1038/nsmb.1440. Epub 2008 Jun 15.
The evolutionary origin of human hepatitis delta virus (HDV) replication by RNA-directed transcription is unclear. Here we identify two species of 5'-capped, approximately 18-25-nucleotide small RNAs. One was of antigenomic polarity, corresponding to the 5' end of hepatitis delta antigen (HDAg) mRNA, and interacted with HDAg and RNA polymerase II (Pol II), whereas the other mapped to a structurally analogous region on the genomic RNA hairpin. An HDAg-interaction screen indicated that HDAg interacts with MOV10, the human homolog of the Arabidopsis thaliana RNA amplification factor gene SDE3 and Drosophila melanogaster RISC-maturation factor gene Armitage (armi). MOV10 knockdown inhibited HDV replication, but not HDAg mRNA translation, further supporting a role for MOV10 in RNA-directed transcription. Together, our studies define RNA hairpins as critical elements for the initiation of HDV-related, RNA-directed transcription. The identification of capped small RNAs and the involvement of MOV10 in HDV replication further suggest a conserved mechanism related to RNA-directed transcription in lower eukaryotes.
人类丁型肝炎病毒（HDV）通过RNA指导的转录进行复制的进化起源尚不清楚。在此，我们鉴定出两种5'-帽化的、长度约为18 - 25个核苷酸的小RNA。一种具有反基因组极性，对应于丁型肝炎抗原（HDAg）mRNA的5'端，并与HDAg和RNA聚合酶II（Pol II）相互作用，而另一种定位于基因组RNA发夹结构上的类似区域。一项HDAg相互作用筛选表明，HDAg与MOV10相互作用，MOV10是拟南芥RNA扩增因子基因SDE3和果蝇RISC成熟因子基因Armitage（armi）的人类同源物。敲低MOV10会抑制HDV复制，但不影响HDAg mRNA的翻译，这进一步支持了MOV10在RNA指导的转录中的作用。总之，我们的研究将RNA发夹定义为HDV相关的RNA指导转录起始的关键元件。帽化小RNA的鉴定以及MOV10参与HDV复制进一步表明，在低等真核生物中存在与RNA指导转录相关的保守机制。
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