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Norovirus genome circularization and efficient replication are facilitated by binding of PCBP2 and hnRNP A1.

Abstract：

:Sequences and structures within the terminal genomic regions of plus-strand RNA viruses are targets for the binding of host proteins that modulate functions such as translation, RNA replication, and encapsidation. Using murine norovirus 1 (MNV-1), we describe the presence of long-range RNA-RNA interactions that were stabilized by cellular proteins. The proteins potentially responsible for the stabilization were selected based on their ability to bind the MNV-1 genome and/or having been reported to be involved in the stabilization of RNA-RNA interactions. Cell extracts were preincubated with antibodies against the selected proteins and used for coprecipitation reactions. Extracts treated with antibodies to poly(C) binding protein 2 (PCBP2) and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 significantly reduced the 5'-3' interaction. Both PCBP2 and hnRNP A1 recombinant proteins stabilized the 5'-3' interactions and formed ribonucleoprotein complexes with the 5' and 3' ends of the MNV-1 genomic RNA. Mutations within the 3' complementary sequences (CS) that disrupt the 5'-3'-end interactions resulted in a significant reduction of the viral titer, suggesting that the integrity of the 3'-end sequence and/or the lack of complementarity with the 5' end is important for efficient virus replication. Small interfering RNA-mediated knockdown of PCBP2 or hnRNP A1 resulted in a reduction in virus yield, confirming a role for the observed interactions in efficient viral replication. PCBP2 and hnRNP A1 induced the circularization of MNV-1 RNA, as revealed by electron microscopy. This study provides evidence that PCBP2 and hnRNP A1 bind to the 5' and 3' ends of the MNV-1 viral RNA and contribute to RNA circularization, playing a role in the virus life cycle.

journal_name

J Virol

journal_title

Journal of virology

authors

López-Manríquez E,Vashist S,Ureña L,Goodfellow I,Chavez P,Mora-Heredia JE,Cancio-Lonches C,Garrido E,Gutiérrez-Escolano AL

doi

10.1128/JVI.03433-12

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

11371-87

issue

eissn

0022-538X

issn

1098-5514

pii

JVI.03433-12

journal_volume

pub_type

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Norovirus genome circularization and efficient replication are facilitated by binding of PCBP2 and hnRNP A1.