Double-stranded RNA viruses of Saccharomyces cerevisiae

The L-A double-stranded RNA virus of Saccharomyces cerevisiae has a 4.6-kb single-segment genome encapsidated in an icosahedral T = 1 particle whose asymmetric element is a dimer of Gag the major coat protein. L-A encodes Gag and its RNA-dependent RNA polymerase (Pol), the latter formed as a Gag-Pol fusion protein produced by a -1 ribosomal frameshift. The efficiency of ribosomal frameshifting is important for viral propagation and is controlled by the host MOF genes. In vitro template-dependent, viral RNA-specific, RNA-binding replication and transcription systems have been wed to study the mechanisms of these reactions. The packaging site on viral plus strands and the part of the Pol domain of the Gag-Pol fusion protein that recognizes it have been defined. The viral transcripts lack both 5' cap structure and 3' poly(A). The host SKI2, SKI3, and SKI8 genes limit viral propagation by blocking the translation of non-poly(A) mRNA. The host SKI1/XRN1 gene encodes a 5' --> 3' exoribonuclease specific for uncapped mRNA and known to be involved ill mRNA turnover. Its action on the uncapped viral mRNA is limited by the cap removal activity of the viral Gag protein acting on cellular mRNAs. M double-stranded RNAs, satellites of L-A, encode secreted ''killer'' toxins as a preprotein. The processing of the preprotoxin is carried out by the Kex1p and Kex2p proteases. The discovery of these genes in this system led to the discovery of mammalian prohormone processing enzymes. Yeast genetics enables detailed dissection of host-virus interactions, most of which probably have homologs in mammalian systems.