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Title: Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase

Abstract

Viruses have various mechanisms to duplicate their genomes and produce virus-specific mRNAs. Negative-strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from members of the Rhabdoviridae, Paramyxoviridae, and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8-Å resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not for mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, including segmented negative-strand RNA and double-stranded RNA (dsRNA) viruses. Negative-strand RNA viruses include a diverse set of viral families that infect animals and plants, causing serious illness and economic impact. Furthermore, the members of this group of viruses share a set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is themore » viral polymerase, which performs a unique set of reactions to produce genome- and subgenome-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative-strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and that shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative-strand RNA viruses.« less

Authors:
 [1];  [2];  [3];  [2];  [1]
  1. Univ. of Alabama, Birmingham, AL (United States)
  2. Case Western Reserve Univ., Cleveland, OH (United States)
  3. Georgia State Univ., Atlanta, GA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH); National Center for Research Resources, Biomedical Technology Program; National Inst. of General Medical Sciences
OSTI Identifier:
1242301
Grant/Contract Number:  
W-31-109-Eng-38; 1R56AI101087; 1R01AI116738; R01AI093569
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Journal of Virology
Additional Journal Information:
Journal Volume: 90; Journal Issue: 2; Journal ID: ISSN 0022-538X
Publisher:
American Society for Microbiology
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Qiu, Shihong, Ogino, Minako, Luo, Ming, Ogino, Tomoaki, and Green, Todd J. Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase. United States: N. p., 2015. Web. doi:10.1128/JVI.02317-15.
Qiu, Shihong, Ogino, Minako, Luo, Ming, Ogino, Tomoaki, & Green, Todd J. Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase. United States. doi:10.1128/JVI.02317-15.
Qiu, Shihong, Ogino, Minako, Luo, Ming, Ogino, Tomoaki, and Green, Todd J. Wed . "Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase". United States. doi:10.1128/JVI.02317-15. https://www.osti.gov/servlets/purl/1242301.
@article{osti_1242301,
title = {Structure and Function of the N-Terminal Domain of the Vesicular Stomatitis Virus RNA Polymerase},
author = {Qiu, Shihong and Ogino, Minako and Luo, Ming and Ogino, Tomoaki and Green, Todd J.},
abstractNote = {Viruses have various mechanisms to duplicate their genomes and produce virus-specific mRNAs. Negative-strand RNA viruses encode their own polymerases to perform each of these processes. For the nonsegmented negative-strand RNA viruses, the polymerase is comprised of the large polymerase subunit (L) and the phosphoprotein (P). L proteins from members of the Rhabdoviridae, Paramyxoviridae, and Filoviridae share sequence and predicted secondary structure homology. Here, we present the structure of the N-terminal domain (conserved region I) of the L protein from a rhabdovirus, vesicular stomatitis virus, at 1.8-Å resolution. The strictly and strongly conserved residues in this domain cluster in a single area of the protein. Serial mutation of these residues shows that many of the amino acids are essential for viral transcription but not for mRNA capping. Three-dimensional alignments show that this domain shares structural homology with polymerases from other viral families, including segmented negative-strand RNA and double-stranded RNA (dsRNA) viruses. Negative-strand RNA viruses include a diverse set of viral families that infect animals and plants, causing serious illness and economic impact. Furthermore, the members of this group of viruses share a set of functionally conserved proteins that are essential to their replication cycle. Among this set of proteins is the viral polymerase, which performs a unique set of reactions to produce genome- and subgenome-length RNA transcripts. In this article, we study the polymerase of vesicular stomatitis virus, a member of the rhabdoviruses, which has served in the past as a model to study negative-strand RNA virus replication. We have identified a site in the N-terminal domain of the polymerase that is essential to viral transcription and that shares sequence homology with members of the paramyxoviruses and the filoviruses. Newly identified sites such as that described here could prove to be useful targets in the design of new therapeutics against negative-strand RNA viruses.},
doi = {10.1128/JVI.02317-15},
journal = {Journal of Virology},
issn = {0022-538X},
number = 2,
volume = 90,
place = {United States},
year = {2015},
month = {12}
}

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    Works referencing / citing this record:

    RNA Synthesis and Capping by Non-segmented Negative Strand RNA Viral Polymerases: Lessons From a Prototypic Virus
    journal, July 2019


    RNA Synthesis and Capping by Non-segmented Negative Strand RNA Viral Polymerases: Lessons From a Prototypic Virus
    journal, July 2019