Evidence that the SKI Antiviral System of Saccharomyces cerevisiae Acts by Blocking Expression of Viral mRNA

Abstract

The SKI2 gene is part of a host system that represses the copy number of the L-A double-stranded RNA (dsRNA) virus and its satellites M and X dsRNA, of the L-BC dsRNA virus, and of the single-stranded replicon 20S RNA. We show that SKI2 encodes a 145-kDa protein with motifs characteristic of helicases and nucleolar proteins and is essential only in cells carrying M dsRNA. Unexpectedly, Ski2p does not repress M1 dsRNA copy number when M1 is supported by aN L-A cDNA clone; nonetheless, it did lower the levels of M1 dsRNA-encoded toxin produced. Since toxin secretion from cDNA clones of M1 is unaffected by Ski2p, these data suggest that Ski2p acts by specifically blocking translation of viral mRNAs, perhaps recognizing the absence of cap or poly(A). In support of this idea, we find that Ski2p represses production of beta-galactosidase from RNA polymerase I [no cap and no poly(A)] transcripts but not from RNA polymerase II (capped) transcripts.

Ski7p G protein interacts with the exosome and the Ski complex for 3'-to-5' mRNA decay in yeast

“…Subsequent studies demonstrated that, in addition to the exosome, the products of SKI2 , SKI3 and SKI8 genes are required for the 3′‐mRNA degradation (Jacobs Anderson and Parker, 1998). Ski2p, Ski3p and Ski8p are a putative RNA helicase, a tetratricopeptide‐repeat protein and a protein containing WD motif, respectively (Rhee et al ., 1989; Matsumoto et al ., 1993; Widner and Wickner, 1993). The three Ski proteins form a stable complex, and the complex is localized in the cytoplasm (Brown et al ., 2000).…”

Unique Terminal Regions and Specific Deletions of the Segmented Double-Stranded RNA Genome of Alternaria Alternata Virus 1, in the Proposed Family Alternaviridae

“…In the future, we would like to investigate what advantages are provided by the cap and poly(A) structures on the AaV1 dsRNA genomic segments. The SKI genes are involved in 5'-3' and 3'-5' mRNA degradation pathways (Toh-E et al, 1978;Widner and Wickner, 1993;. Therefore, we will utilize SKI-deficient mutants or SKI-overexpressing strains of Saccharomyces cerevisiae, since this might provide valuable insights into the roles of the cap and poly(A) structures in RNA degradation.…”

Adaptive Response of Saccharomyces Hosts to Totiviridae L-A dsRNA Viruses Is Achieved through Intrinsically Balanced Action of Targeted Transcription Factors

“…Numerous TFs are involved in this complex regulatory network. The virus might act towards the activation of genes required for its replication (e.g., MAK3, MAK10, and MAK31 [17,21,22]), whereas the host may induce the expression of genes involved in virus suppression (e.g., XRN1/SKI1, SKI2, SKI3, SKI7, SKI8, NUC1, and POR1/2 [28,33,44,45]) to control virus propagation and vice versa. Similarly, the virus may contribute to the repression of the transcription of genes conflicting with its functioning; similarly, the host might inhibit the expression of genes that aid the virus.…”

“…L-A virus propagation is controlled or inhibited by systems found in yeast cells. Nascent L-A mRNA has neither cap nor polyA tails [32]; thus, its 5 -end is prone to degradation by exonuclease Xrn1/Ski1, whereas cytoplasmic exosome degrades mRNA, which lacks a polyA tail in the 3 -end [12,33]. Xrn1 is involved in the regulation of various cellular processes, including meiosis [34], filamentous growth [35], RNA turnover [36], control of telomere length [37], respiration [38], and autophagy [39].…”

“…The action of the exosome is linked to the SKI complex, in which Ski2, Ski3, Ski7, and Ski8 proteins are required for the proper identification of exosome targets (see [40] for review). The disruption of any of these SKI genes enables higher levels of viral dsRNA; in case of the presence of M virus, markedly higher production of killer toxin, leading to the so-called "superkiller" phenotype [33]. To avoid these mechanisms, the virus has developed protection strategies.…”