Quality control of mRNA 3′-end processing is linked to the nuclear exosome

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Abstract
An emerging theme in messenger RNA metabolism is the coupling of nuclear pre-mRNA processing events, which contributes to mRNA quality control1. Most eukaryotic mRNAs acquire a poly(A) tail during 3′-end processing within the nucleus, and this is coupled to efficient export of mRNAs to the cytoplasm2,3. In the yeast Saccharomyces cerevisiae, a common consequence of defective nuclear export of mRNA is the hyperadenylation of nascent transcripts4,5, which are sequestered at or near their sites of transcription5. This implies that polyadenylation and nuclear export are coupled in a step that involves the release of mRNA from transcription site foci. Here we demonstrate that transcripts which fail to acquire a poly(A) tail are also retained at or near transcription sites. Surprisingly, this retention mechanism requires the protein Rrp6p and the nuclear exosome, a large complex of exonucleolytic enzymes6,7. In exosome mutants, hypo- as well as hyperadenylated mRNAs are released and translated. These observations suggest that the exosome contributes to a checkpoint that monitors proper 3′-end formation of mRNA.