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Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase

  作者 Morin, B; Rahmeh, AA; Whelan, SPJ  
  选自 期刊  EMBO journal;  卷期  2012年31-5;  页码  1320-1329  
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[摘要]The minimal RNA synthesis machinery of non-segmented negative-strand RNA viruses comprises a genomic RNA encased within a nucleocapsid protein (N-RNA), and associated with the RNA-dependent RNA polymerase (RdRP). The RdRP is contained within a viral large (L) protein, which associates with N-RNA through a phosphoprotein (P). Here, we define that vesicular stomatitis virus L initiates synthesis via a de-novo mechanism that does not require N or P, but depends on a high concentration of the first two nucleotides and specific template requirements. Purified L copies a template devoid of N, and P stimulates L initiation and processivity. Full processivity of the polymerase requires the template-associated N protein. This work provides new mechanistic insights into the workings of a minimal RNA synthesis machine shared by a broad group of important human, animal and plant pathogens, and defines a mechanism by which specific inhibitors of RNA synthesis function. The EMBO Journal (2012) 31, 1320-1329. doi:10.1038/emboj.2011.483; Published online 13 January 2012

 
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