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Chikungunya virus nonstructural protein 1 is a versatile RNA capping and decapping enzyme.


ABSTRACT: Chikungunya virus (CHIKV) nonstructural protein 1 (nsP1) contains both the N7-guanine methyltransferase and guanylyltransferase activities and catalyzes the 5' end cap formation of viral RNAs. To further understand its catalytic activity and role in virus-host interaction, we demonstrate that purified recombinant CHIKV nsP1 can reverse the guanylyl transfer reaction and remove the m7GMP from a variety of capped RNA substrates including host mRNAs. We then provide the structural basis of this function with a high-resolution cryo-EM structure of nsP1 in complex with the unconventional cap-1 substrate RNA m7GpppAmU. We show that the 5'ppRNA species generated by decapping can trigger retinoic acid-inducible gene I-mediated interferon response. We further demonstrate that the decapping activity is conserved among the alphaviral nsP1s. To our knowledge, this is a new mechanism through which alphaviruses activate the antiviral immune response. This decapping activity could promote cellular mRNA degradation and facilitate viral gene expression, which is functionally analogous to the cap-snatching mechanism by influenza virus.

SUBMITTER: Law MCY 

PROVIDER: S-EPMC10687048 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Chikungunya virus nonstructural protein 1 is a versatile RNA capping and decapping enzyme.

Law Michelle Cheok Yien MCY   Zhang Kuo K   Tan Yaw Bia YB   Nguyen Trinh Mai TM   Luo Dahai D  

The Journal of biological chemistry 20231031 12


Chikungunya virus (CHIKV) nonstructural protein 1 (nsP1) contains both the N7-guanine methyltransferase and guanylyltransferase activities and catalyzes the 5' end cap formation of viral RNAs. To further understand its catalytic activity and role in virus-host interaction, we demonstrate that purified recombinant CHIKV nsP1 can reverse the guanylyl transfer reaction and remove the m<sup>7</sup>GMP from a variety of capped RNA substrates including host mRNAs. We then provide the structural basis  ...[more]

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