Messenger RNA turnover and its regulation in herpesviral infection.
The ability to regulate cellular gene expression is a key aspect of the lifecycles of a diverse array of viruses. In fact, viral infection often results in a global shutoff of host cellular gene expression; such inhibition serves not only to ensure maximal viral gene expression without competition from the host for essential machinery and substrates but also aids in evasion of immune responses detrimental to successful viral replication and dissemination. Within the herpesvirus family, host shutoff is a prominent feature of both the alpha- and gamma-herpesviruses. Intriguingly, while both classes of herpesviruses block cellular gene expression by inducing decay of messenger RNAs, the viral factors responsible for this phenotype as well as the mechanisms by which it is achieved are quite distinct. However, data suggest that the host shutoff functions of alpha- and gamma-herpesviruses are likely achieved both through the activity of virally encoded nucleases as well as via modulation of cellular RNA degradation pathways. This review highlights the processes governing normal cellular messenger RNA decay and then details the mechanisms by which herpesviruses promote accelerated RNA turnover. Parallels between the viral and cellular degradation systems as well as the known interactions between viral host shutoff factors and the cellular RNA turnover machinery are highlighted.
Glaunsinger
Britt A
BA
Howard Hughes Medical Institute, Department of Microbiology, University of California, San Francisco, 94143, USA.
Ganem
Donald E
DE
D000818:Animals; D005786:Gene Expression Regulation; D015967:Gene Expression Regulation, Viral; D006564:Herpesviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000821:virology; D006801:Humans; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
D012333:RNA, Messenger