Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus

Amal A. Rahmeh, Benjamin Morin, Andreas D. Schenk, Bo Liang, Bianca S. Heinrich, Vesna Brusic, Thomas Walz, Sean P.J. Whelan

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


The RNA-dependent RNA polymerase (RdRP) of nonsegmented negative-sense RNA viruses consists of a large catalytic protein (L) and a phosphoprotein cofactor (P). During infection, the RdRP replicates and transcribes the viral genome, which resides inside an oligomer of nucleocapsid protein (N-RNA). The classical view of P as a cofactor for L assigns a primary role of P as a bridge mediating the access of L to the RNA template, whereby its N-terminal domain (PNTD) binds L and its C-terminal domain (PCTD) binds NRNA. Recent biochemical and structural studies of a prototype nonsegmented negative-sense RNA virus, vesicular stomatitis virus, suggest a role for P beyond that of a mere physical link: P induces a structural rearrangement in L and stimulates polymerase processivity. In this study, we investigated the critical requirements within P mediating the functional interaction with L to form a fully functional RdRP. We analyzed the correlation between the impact of P on the conformation of L and its activity in RNA synthesis and the consequences of these events on RdRP function. We identified three separable elements of the PNTD that are required for inducing the conformational rearrangement of L, stimulating polymerase processivity, and mediating transcription of the NRNA. The functional interplay between these elements provides insight into the role of P as a dynamic player in the RNA synthesis machine, influencing essential aspects of polymerase structure and function.

Original languageEnglish
Pages (from-to)14628-14633
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number36
StatePublished - Sep 4 2012


  • Large polymerase
  • Mononegavirales
  • Replication and transcription
  • Rhabdovirus


Dive into the research topics of 'Critical phosphoprotein elements that regulate polymerase architecture and function in vesicular stomatitis virus'. Together they form a unique fingerprint.

Cite this