Cap-binding protein 1-mediated and eukaryotic translation initiation factor 4E-mediated pioneer rounds of translation in yeast

Nonsense-mediated mRNA decay (NMD) in mammalian cells is restricted to newly synthesized mRNA that is bound at the 5' cap by the major nuclear cap-binding complex and at splicing-generated exon-exon junctions by exon junction complexes. This messenger ribonucleoprotein has been called the pioneer translation initiation complex and, accordingly, NMD occurs as a consequence of nonsense codon recognition during a pioneer round of translation. Here, we characterize the nature of messenger ribonucleoprotein that is targeted for NMD in Saccharomyces cerevisiae. Data indicate that NMD targets both cap-binding complex (Cbc)1p- and eukaryotic translation initiation factor (elF)4E-bound mRNAs, unlike in mammalian cells, where NMD does not detectably target elF4E-bound mRNA. First, intron-containing pre-mRNAs in yeast are detectably bound by either Cbc1p, or, unlike in mammalian cells, elF4E, indicating that mRNAs can be derived from either Cbc1p- or elF4E-bound pre-mRNAs. Second, the ratio of nonsense-containing Cbc1p-bound mRNA to nonsense-free Cbc1p-bound mRNA, which was < 0.4 for those mRNAs tested here, is essentially identical to the ratio of the corresponding nonsense-containing elF4E-bound mRNA to nonsense-free elF4E-bound mRNA, and both ratios increase in cells treated with the translational inhibitor cycloheximide (CHX). These data, together with data presented here and elsewhere showing that Cbc1p-bound transcripts are precursors to elF4E-bound transcripts, demonstrate that Cbc1p-bound mRNA is targeted for NMD. In support of the idea that elF4E-bound mRNA is also targeted for NMD, elF4E-bound mRNA is targeted for NMD in strains that lack Cbc1p. These results suggest that both Cbc1p- and elF4E-mediated pioneer rounds of translation occur in yeast.