Nucleotide triphosphatase and RNA chaperone activities of murine norovirus NS3

Han, Kang Rok and Lee, Ji-Hye and Kotiguda, Giri Gowda and Jung, Kyoung Ho and Chung, Mi Sook and Kang, Soowon and Hwang, Seungmin and Kim, Kyung Hyun (2018) Nucleotide triphosphatase and RNA chaperone activities of murine norovirus NS3. In: JOURNAL OF GENERAL VIROLOGY, 99 (11). pp. 1482-1493.

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Abstract

Modulation of RNA structure is essential in the life cycle of RNA viruses. Immediate replication upon infection requires RNA unwinding to ensure that RNA templates are not in intra-or intermolecular duplex forms. The calicivirus NS3, one of the highly conserved nonstructural (NS) proteins, has conserved motifs common to helicase superfamily 3 among six genogroups. However, its biological functions are not fully understood. In this study we report the oligomeric state and the nucleotide triphosphatase (NTPase) and RNA chaperone activities of the recombinant full-length NS3 derived from murine norovirus (MNV). The MNV NS3 has an Mg2+-dependent NTPase activity, and site-directed mutagenesis of the conserved NTPase motifs blocked enzyme activity and viral replication in cells. Further, the NS3 was found via fluorescence resonance energy transfer (FRET)-based assays to destabilize double-stranded RNA in the presence of Mg2+ or Mn2+ in an NTP-independent manner. However, the RNA destabilization activity was not affected by mutagenesis of the conserved motifs of NTPase. These results reveal that the MNV NS3 has an NTPase-independent RNA chaperone-like activity, and that a FRET-based RNA destabilization assay has the potential to identify new antiviral drugs targeting NS3.

Item Type:	Journal Article
Publication:	JOURNAL OF GENERAL VIROLOGY
Publisher:	MICROBIOLOGY SOC
Additional Information:	Copy right for this article belong to MICROBIOLOGY SOC
Keywords:	norovirus; RNA replication; NS3; NTPase; helicase; RNA chaperone
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	20 Nov 2018 17:27
Last Modified:	20 Nov 2018 17:27
URI:	http://eprints.iisc.ac.in/id/eprint/61109

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