| Structural highlights
Function
[L_VSIVA] RNA-directed RNA polymerase that catalyzes the transcription of viral mRNAs, their caping and polyadenylation (PubMed:24526687). The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The viral polymerase binds to the genomic RNA at the 3' leader promoter, and transcribes subsequently all viral mRNAs with a decreasing efficiency. The first gene is the most transcribed, and the last the least transcribed. The viral phosphoprotein acts as a processivity factor (PubMed:22908284). Caping is concommitant with initiation of mRNA transcription. The polymerase mRNA guanylyl transferase displays a different biochemical reaction than the cellular enzyme (PubMed:21945214). Polyadenylation of mRNAs occur by a stuttering mechanism at a slipery stop site present at the end viral genes. After finishing transcription of a mRNA, the polymerase can resume transcription of the downstream gene.[1] [2] [3] [4] [5] RNA-directed RNA polymerase that catalyzes the replication of viral genomic RNA. The template is composed of the viral RNA tightly encapsidated by the nucleoprotein (N). The replicase mode is dependent on intracellular N protein concentration. In this mode, the polymerase replicates the whole viral genome without recognizing transcriptional signals, and the replicated genome is not caped or polyadenylated.[6] [7] [8] [9]
Publication Abstract from PubMed
The large (L) proteins of non-segmented, negative-strand RNA viruses, a group that includes Ebola and rabies viruses, catalyze RNA-dependent RNA polymerization with viral ribonucleoprotein as template, a non-canonical sequence of capping and methylation reactions, and polyadenylation of viral messages. We have determined by electron cryomicroscopy the structure of the vesicular stomatitis virus (VSV) L protein. The density map, at a resolution of 3.8 A, has led to an atomic model for nearly all of the 2109-residue polypeptide chain, which comprises three enzymatic domains (RNA-dependent RNA polymerase [RdRp], polyribonucleotidyl transferase [PRNTase], and methyltransferase) and two structural domains. The RdRp resembles the corresponding enzymatic regions of dsRNA virus polymerases and influenza virus polymerase. A loop from the PRNTase (capping) domain projects into the catalytic site of the RdRp, where it appears to have the role of a priming loop and to couple product elongation to large-scale conformational changes in L.
Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy.,Liang B, Li Z, Jenni S, Rahmeh AA, Morin BM, Grant T, Grigorieff N, Harrison SC, Whelan SP Cell. 2015 Jul 16;162(2):314-27. doi: 10.1016/j.cell.2015.06.018. Epub 2015 Jul, 2. PMID:26144317[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Banerjee AK, Chattopadhyay D. Structure and function of the RNA polymerase of vesicular stomatitis virus. Adv Virus Res. 1990;38:99-124. PMID:2171304
- ↑ Ogino T, Banerjee AK. An unconventional pathway of mRNA cap formation by vesiculoviruses. Virus Res. 2011 Dec;162(1-2):100-9. doi: 10.1016/j.virusres.2011.09.012. Epub, 2011 Sep 16. PMID:21945214 doi:http://dx.doi.org/10.1016/j.virusres.2011.09.012
- ↑ Morin B, Rahmeh AA, Whelan SP. Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase. EMBO J. 2012 Mar 7;31(5):1320-9. doi: 10.1038/emboj.2011.483. Epub 2012 Jan 13. PMID:22246179 doi:http://dx.doi.org/10.1038/emboj.2011.483
- ↑ Rahmeh AA, Morin B, Schenk AD, Liang B, Heinrich BS, Brusic V, Walz T, Whelan SP. Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14628-33. doi:, 10.1073/pnas.1209147109. Epub 2012 Aug 20. PMID:22908284 doi:http://dx.doi.org/10.1073/pnas.1209147109
- ↑ Morin B, Whelan SP. Sensitivity of the polymerase of vesicular stomatitis virus to 2' substitutions in the template and nucleotide triphosphate during initiation and elongation. J Biol Chem. 2014 Apr 4;289(14):9961-9. doi: 10.1074/jbc.M113.542761. Epub 2014, Feb 13. PMID:24526687 doi:http://dx.doi.org/10.1074/jbc.M113.542761
- ↑ Banerjee AK, Chattopadhyay D. Structure and function of the RNA polymerase of vesicular stomatitis virus. Adv Virus Res. 1990;38:99-124. PMID:2171304
- ↑ Morin B, Rahmeh AA, Whelan SP. Mechanism of RNA synthesis initiation by the vesicular stomatitis virus polymerase. EMBO J. 2012 Mar 7;31(5):1320-9. doi: 10.1038/emboj.2011.483. Epub 2012 Jan 13. PMID:22246179 doi:http://dx.doi.org/10.1038/emboj.2011.483
- ↑ Rahmeh AA, Morin B, Schenk AD, Liang B, Heinrich BS, Brusic V, Walz T, Whelan SP. Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2012 Sep 4;109(36):14628-33. doi:, 10.1073/pnas.1209147109. Epub 2012 Aug 20. PMID:22908284 doi:http://dx.doi.org/10.1073/pnas.1209147109
- ↑ Morin B, Whelan SP. Sensitivity of the polymerase of vesicular stomatitis virus to 2' substitutions in the template and nucleotide triphosphate during initiation and elongation. J Biol Chem. 2014 Apr 4;289(14):9961-9. doi: 10.1074/jbc.M113.542761. Epub 2014, Feb 13. PMID:24526687 doi:http://dx.doi.org/10.1074/jbc.M113.542761
- ↑ Liang B, Li Z, Jenni S, Rahmeh AA, Morin BM, Grant T, Grigorieff N, Harrison SC, Whelan SP. Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy. Cell. 2015 Jul 16;162(2):314-27. doi: 10.1016/j.cell.2015.06.018. Epub 2015 Jul, 2. PMID:26144317 doi:http://dx.doi.org/10.1016/j.cell.2015.06.018
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