The L-A double-stranded RNA virus of Saccharomyces cerevisiae encodes its major coat protein (Gag) and a multifunctional Pol domain expressed only as a Gag-Pol fusion protein formed by a -1 ribosomal frameshift. The frameshift event occurs by a mechanism identical too that used by retroviruses to form their own Gag-Pol fusion proteins. We have found that the 5S rRNA affects the efficiency of frameshifting, as do several other cellular genes. The L-A virus decaps cellular mRNAs in order to form decoys to distract the cellular XRN1- encoded 5' exoribonuclease specific for uncapped RNAs from degrading the viral mRNA. The yeast SKI2,3,8 system represses viral replication by limiting the translation of non-poly(A) mRNAs, such s that of L-A. We propose that the SKI2,3,8 system prepares 60S ribosomal subunits to make them require interaction with the 3' poly(A) before they will bind to the 40S subunit waiting at the initiator AUG. We find that of 27 genes (MAK genes) required for propagation of M1 dsRNA (a satellite of L-A), mutants in 20 are deficient in 60S ribosomal subunits. Some encode proteins of the large ribosomal subunit (MAK7 + RPL4A; MAK8 = RPL3; MAK18 = RPL41B) while others do not. We suggest that non-poly(A) mRNAs are at a disadvantage in competing for 60S subunits. We describe the first dsRNA virus of a human pathogenic fungus, Blastomyces dermatitidis.
