Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase |
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Authors: | Morin Benjamin Rahmeh Amal A Whelan Sean P J |
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Institution: | Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA. |
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Abstract: | 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. |
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Keywords: | de‐novo RNA synthesis initiation negative‐strand RNA viruses ribavirin RNA‐dependent RNA polymerases vesicular stomatitis virus |
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