Viral Interactions with Host RNA Decay Pathways

Eukaryotes have evolved a wide variety of RNA decay pathways to maintain cellular homeostasis, carry out programs of gene expression, and respond to changing environmental conditions. Individual RNA turnover mechanisms can operate constitutively or under only particular cellular conditions; similarly, some target many RNAs, while others act with great specificity. It has become increasingly clear that there are extensive interactions between viruses and the host RNA decay machinery. Often, the cellular RNA decay machinery poses a threat to viral gene expression, but viruses can also manipulate RNA decay pathways to promote viral replication. This special issue focuses on how cellular RNA decay factors recognize and degrade viral RNAs and viral strategies to subvert or evade these pathways

Rous Sarcoma Virus RNA Stability Element Inhibits Deadenylation of mRNAs with Long 3′UTRs

All retroviruses use their full-length primary transcript as the major mRNA for Group-specific antigen (Gag) capsid proteins. This results in a long 3′ untranslated region (UTR) downstream of the termination codon. In the case of Rous sarcoma virus (RSV), there is a 7 kb 3′UTR downstream of the gag terminator, containing the pol, env, and src genes. mRNAs containing long 3′UTRs, like those with premature termination codons, are frequently recognized by the cellular nonsense-mediated mRNA decay (NMD) machinery and targeted for degradation. To prevent this, RSV has evolved an RNA stability element (RSE) in the RNA immediately downstream of the gag termination codon. This 400-nt RNA sequence stabilizes premature termination codons (PTCs) in gag. It also stabilizes globin mRNAs with long 3′UTRs, when placed downstream of the termination codon. It is not clear how the RSE stabilizes the mRNA and prevents decay. We show here that the presence of RSE inhibits deadenylation severely. In addition, the RSE also impairs decapping (DCP2) and 5′-3′ exonucleolytic (XRN1) function in knockdown experiments in human cells

In memoriam Kuan-Teh Jeang (1958-2013): retrovirologist par excellence and founding editor of Retrovirology

Kuan-Teh Jeang MD, PhD, (Teh) died suddenly and unexpectedly on the evening of January 27, 2013, at the age of 54, to the shock of his many friends and colleagues.

The Negative Regulator of Splicing Element of Rous Sarcoma Virus Promotes Polyadenylation

The Rous sarcoma virus gag gene contains a cis-acting negative regulator of splicing (NRS) element that is implicated in viral polyadenylation regulation. To study the mechanism of polyadenylation promotion at the viral poly(A) site located over 8 kb downstream, we performed in vitro polyadenylation analysis. RNA containing only the poly(A) site and flanking sequences in the 3′ long terminal repeat (LTR) was not polyadenylated detectably in vitro; however, if the transcript contained the NRS upstream of the LTR, polyadenylation was observed. Insertion of the viral env 3′ splice site sequence between the NRS and the LTR did not alter the level of polyadenylation appreciably. We conclude that the NRS promotes polyadenylation in vitro and can do so without formation of a splicing complex with a 3′ splice site. We then explored the roles of several cellular factors in NRS-mediated polyadenylation. Mutation of the binding sites of U1 and U11 snRNPs to the NRS did not affect polyadenylation, whereas hnRNP H strongly inhibited polyadenylation. We propose a model in which hnRNP H and SR proteins compete for binding to the NRS. Bound SR proteins may bridge between the NRS and the 3′ LTR and aid in the recruitment of the 3′-end processing machinery