Attacked from All Sides: RNA Decay in Antiviral Defense

Abstract

The innate immune system has evolved a number of sensors that recognize viral RNA (vRNA) to restrict infection, yet the full spectrum of host-encoded RNA binding proteins that target these foreign RNAs is still unknown. The RNA decay machinery, which uses exonucleases to degrade aberrant RNAs largely from the 5' or 3' end, is increasingly recognized as playing an important role in antiviral defense. The 5' degradation pathway can directly target viral messenger RNA (mRNA) for degradation, as well as indirectly attenuate replication by limiting specific pools of endogenous RNAs. The 3' degradation machinery (RNA exosome) is emerging as a downstream effector of a diverse array of vRNA sensors. This review discusses our current understanding of the roles of the RNA decay machinery in controlling viral infection.

Keywords: RNA decay; RNA-protein interactions; RNAse; TRAMP; Xrn1; antiviral; decapping; exonuclease; exosome; intrinsic immunity.

Figure 1

The 5′ to 3′ decay machinery can inhibit viral infection directly through degradation of viral RNA (vRNA; flaviviruses) or indirectly through decapping and degradation of RNAs needed for viral transcription and translation (bunyaviruses). The 3′ to 5′ decay machinery, the RNA exosome, interacts with a variety of RNA-binding proteins, some of which are exported to the cytoplasm in response to viral infection. Recruitment of the exosome can result in degradation of vRNA.