Decoying the cap- mRNA degradation system by a double-stranded RNA virus and poly(A)- mRNA surveillance by a yeast antiviral system.
The major coat protein of the L-A double-stranded RNA virus of Saccharomyces cerevisiae covalently binds m7 GMP from 5' capped mRNAs in vitro. We show that this cap binding also occurs in vivo and that, while this activity is required for expression of viral information (killer toxin mRNA level and toxin production) in a wild-type strain, this requirement is suppressed by deletion of SKI1/XRN1/SEP1. We propose that the virus creates decapped cellular mRNAs to decoy the 5'-->3' exoribonuclease specific for cap- RNA encoded by XRN1. The SKI2 antiviral gene represses the copy numbers of the L-A and L-BC viruses and the 20S RNA replicon, apparently by specifically blocking translation of viral RNA. We show that SKI2, SKI3, and SKI8 inhibit translation of electroporated luciferase and beta-glucuronidase mRNAs in vivo, but only if they lack the 3' poly(A) structure. Thus, L-A decoys the SKI1/XRN1/SEP1 exonuclease directed at 5' uncapped ends, but translation of the L-A poly(A)- mRNA is repressed by Ski2,3,8p. The SKI2-SKI3-SKI8 system is more effective against cap+ poly(A)- mRNA, suggesting a (nonessential) role in blocking translation of fragmented cellular mRNAs.
Masison
D C
DC
Section on Genetics of Simple Eukaryotes, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Blanc
A
A
Ribas
J C
JC
Carroll
K
K
Sonenberg
N
N
Wickner
R B
RB
D002213:Capsid / Q000378:metabolism; D003851:Deoxyribonucleases / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D055646:Killer Factors, Yeast; D008954:Models, Biological; D009183:Mycotoxins / Q000235:genetics; D014176:Protein Biosynthesis; D012315:RNA Caps / Q000235:genetics / Q000378:metabolism*; D012328:RNA Viruses / Q000378:metabolism*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism*; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic
D005656:Fungal Proteins; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D012315:RNA Caps; D012330:RNA, Double-Stranded; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D003851:Deoxyribonucleases; D005095:Exoribonucleases; C068398:XRN1 protein, S cerevisiae