Inhibition of mRNA turnover in yeast by an xrn1 mutation enhances the requirement for eIF4E binding to eIF4G and for proper capping of transcripts byCeg1p

Null mutants: of XRN1, encoding the major cytoplasmic exoribonuclease in ye ast, are viable but accumulate decapped, deadenylated transcripts. A screen for mutations synthetic lethal with xrn1 Delta identified a mutation in CD C33, encoding eIF4E. This mutation (glutamate to glycine at position 72) af fected a highly conserved residue involved in interaction with eIF4G. Synth etic lethality between xrn1 and cdc33 was not relieved by high-copy express ion of eIF4G or by disruption of the yeast eIF4E binding protein Caf20p. Hi gh-copy expression of a mutant eIF4G defective for eIF4E binding resulted i n a dominant negative phenotype in an xrn1 mutant, indicating the importanc e of this inter action in an xrn1 mutant. Another allele of CDC33 cdc33-1, along with mutations in CEG1, encoding the nuclear guanylyltransferase, wer e also synthetic lethal with xrn1 Delta, whereas mutations in PRT1, encodin g a subunit of eIF3, were not. Mutations in CDC33, CEG1, PRT1, PAB1, and TI F4631, encoding eIF4G1, have been shown to lead to destabilization of mRNAs . Although such destabilization in cdc33 ceg1, and pab1 mutants can be part ially suppressed by an xrn1 mutation, we observed synthetic lethality betwe en xrn1 and either cdc33 or ceg1 and no suppression of the inviability of a pab1 null mutation by xnr1 Delta. Thus, the inhibition of mRNA turnover by blocking Xrn1p function does not suppress the lethality of defects upstrea m in the turnover pathway but it does enhance the requirement for (7)mG cap s and for proper formation of the eIF4E/eIF4G cap recognition complex.