Article
- The EMBO Journal (2007) 26, 4566 - 4575
- doi:10.1038/sj.emboj.7601881
Published online: 11 October 2007
Subject Categories:
De novo replication of the influenza virus RNA genome is regulated by DNA replicative helicase, MCM
Atsushi Kawaguchi1 and Kyosuke Nagata1
- Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan
Correspondence to:
Kyosuke Nagata, Department of Infection Biology, Graduate School of Comprehensive Human Sciences and Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan. Tel.: +81 29 853 3233; Fax: +81 29 853 3233; E-mail: knagata@md.tsukuba.ac.jp
Received 12 June 2007; Accepted 18 September 2007
Abstract
By dissecting and reconstituting a cell-free influenza virus genome replication system, we have purified and identified the minichromosome maintenance (MCM) complex, which is thought to be a DNA replicative helicase, as one of the host factors that regulate the virus genome replication. MCM interacted with the PA subunit of the viral RNA-dependent RNA polymerase that is found to be involved in the replication genetically. The virus genome replication was decreased in MCM2 knockdown cells. The viral polymerase appeared to be a nonproductive complex, that is, it was capable of initiating replication but produced only abortive short RNA chains. MCM stimulated de novo-initiated replication reaction by stabilizing a replication complex during its transition from initiation to elongation. Based on the findings, including the result that the MCM-mediated RNA replication reaction was competed with exogenously added RNA, we propose that MCM functions as a scaffold between the nascent RNA chains and the viral polymerase.
Keywords:
- host factor,
- influenza virus,
- MCM,
- replication,
- RNA-dependent RNA polymerase
