Interplay between viruses and host mRNA degradation

Abstract

Messenger RNA degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mRNAs in cells. Naturally, viruses must successfully interface with the robust cellular RNA degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. In the past several years, studies have discovered many elegant strategies that viruses have evolved to circumvent the cellular RNA degradation machinery, ranging from disarming the RNA decay pathways and co-opting the factors governing cellular mRNA stability to promoting host mRNA degradation that facilitates selective viral gene expression and alters the dynamics of host-pathogen interaction. This review summarizes the current knowledge of the multifaceted interaction between viruses and cellular mRNA degradation machinery to provide an insight into the regulatory mechanisms that influence gene expression in viral infections. This article is part of a Special Issue entitled: RNA Decay mechanisms.

Fig. 1

Major pathways of cellular mRNA decay. A) A majority of cellular mRNAs are degraded by the deadenylation-dependent decay pathway. The cellular deadenylase complexes, CCR4-NOT, PARN or PAN2-PAN3 removes the poly(A) tail and subsequently, the body of the deadenylated mRNA is degraded by 5′-3′ or 3′-5′decay mechanisms. In the 5′-3′ decay pathway, the Lsm1-7 protein complex binds to the 3′-end of the deadenylated mRNA and stimulates decapping by the DCP1-DCP2 enzyme complex that generates a monophosphorylated 5′-end. Following decapping, the mRNA body is degraded by the action of the 5′-3′ exoribonuclease, XRN1. Most of the proteins involved in the 5′-3′ decay pathway are localized in P bodies. The 3′-5′ decay of the deadenylated mRNA is catalyzed by the 3′-5′ exoribonucleolytic activity of the exosome followed by the removal of the cap structure by the scavenger decapping enzyme, DCPS. B) The endonuclease-mediated decay pathway triggers the degradation of some mRNAs, including those recognized by cellular mRNA surveillance and stress response pathways like NMD, NGD, RNase L and IRE1. The decay is initiated by an endonuclease cleavage event followed by the digestion of the resulting unprotected fragments by exosome and XRN1. The figure is adapted from Fig. 1 in Ref. . Selected examples of viral proteins that interfere with the cellular mRNA decay machinery are provided. See text for details. * denotes that the SARS-CoV nsp1-induced endonuclease activity could be host-encoded.

Fig. 2

Schematic representation of the viral evasion mechanisms. Examples of the various strategies of viral evasion of the cellular mRNA decay pathways. A description of these examples is provided in the text. PV, poliovirus.

Fig. 3

Schematic representation of the viral subversion mechanisms. Selected examples of the viral mechanisms to subvert and exploit the cellular mRNA decay machinery. Mechanistic details are provided in the text. * denotes that the SARS-CoV nsp1-induced endonuclease activity could be host-encoded.