Pat1 globally activates deadenylation-dependent decapping to clear inefficiently translated oligo(A)-tailed transcripts

Abstract

In eukaryotes, mRNA turnover occurs mainly through the 5'- 3' mRNA decay pathway and involves deadenylation, decapping, and exonucleolytic mRNA body digestion. While the conserved protein Pat1 has initially been described as an activator of decapping for some deadenylated mRNAs, the role of deadenylation-dependent decapping has recently been questioned. Hence, Pat1 has alternatively been suggested to regulate specific mRNA decay pathways, given its modest impact on overall transcriptome composition. Here, we combine multi-omic and genetic approaches to characterize a PAT1 deletion mutant in Saccharomyces cerevisiae. Although transcriptome and proteome analyses confirm that only a limited subset of genes is affected by Pat1 inactivation, poly(A)-tail sizing demonstrates that Pat1 loss leads to transcriptome-wide accumulation of capped oligo(A)-tailed mRNAs. Together with the observation that oligo(A)-tailed mRNAs are bound by Pat1 in vivo in wild-type cells, this indicates that Pat1 is a general activator of deadenylation-dependent decapping. We further show that oligo-adenylated mRNAs are translated in {Delta}pat1 cells, albeit inefficiently. Altogether, our data indicate that Pat1 mediates the clearance of oligo(A)-tailed mRNAs protecting cells from the ensuing inefficient translation, without inducing major changes in overall transcript distribution.

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• biorxiv v1 2026-10-23 source ↗

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