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Virus Res. 2017 Apr 15;234:135-152. doi: 10.1016/j.virusres.2017.01.006. Epub 2017 Jan 16.

Cystoviral RNA-directed RNA polymerases: Regulation of RNA synthesis on multiple time and length scales.

Author information

1
Department of Chemistry and Biochemistry, The City College of New York, New York, NY 10031, United States. Electronic address: salphonse@ccny.cuny.edu.
2
Department of Chemistry and Biochemistry, The City College of New York, New York, NY 10031, United States; Graduate Programs in Biochemistry, The Graduate Center of CUNY, New York, NY 10016, United States; Graduate Programs in Chemistry, The Graduate Center of CUNY, New York, NY 10016, United States; Graduate Programs in Physics, The Graduate Center of CUNY, New York, NY 10016, United States. Electronic address: rghose@ccny.cuny.edu.

Abstract

P2, an RNA-directed RNA polymerase (RdRP), is encoded on the largest of the three segments of the double-stranded RNA genome of cystoviruses. P2 performs the dual tasks of replication and transcription de novo on single-stranded RNA templates, and plays a critical role in the viral life-cycle. Work over the last few decades has yielded a wealth of biochemical and structural information on the functional regulation of P2, on its role in the spatiotemporal regulation of RNA synthesis and its variability across the Cystoviridae family. These range from atomic resolution snapshots of P2 trapped in functionally significant states, in complex with catalytic/structural metal ions, polynucleotide templates and substrate nucleoside triphosphates, to P2 in the context of viral capsids providing structural insight into the assembly of supramolecular complexes and regulatory interactions therein. They include in vitro biochemical studies using P2 purified to homogeneity and in vivo studies utilizing infectious core particles. Recent advances in experimental techniques have also allowed access to the temporal dimension and enabled the characterization of dynamics of P2 on the sub-nanosecond to millisecond timescale through measurements of nuclear spin relaxation in solution and single molecule studies of transcription from seconds to minutes. Below we summarize the most significant results that provide critical insight into the role of P2 in regulating RNA synthesis in cystoviruses.

KEYWORDS:

Bacteriophage; Cystovirus; RNA-directed RNA polymerase; Replication; Transcription

PMID:
28104452
PMCID:
PMC5476504
DOI:
10.1016/j.virusres.2017.01.006
[Indexed for MEDLINE]
Free PMC Article

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