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

An emerging theme in messenger RNA metabolism is the coupling of nuclear pr e-mRNA processing events, which contributes to mRNA quality control(1). Mos t eukaryotic mRNAs acquire a poly(A) tail during 3'-end processing within t he nucleus, and this is coupled to efficient export of mRNAs to the cytopla sm(2,3). In the yeast Saccharomyces cerevisiae, a common consequence of def ective nuclear export of mRNA is the hyperadenylation of nascent transcript s(4,5), which are sequestered at or near their sites of transcription(5). T his implies that polyadenylation and nuclear export are coupled in a step t hat involves the release of mRNA from transcription site foci. Here we demo nstrate that transcripts which fail to acquire a poly(A) tail are also reta ined at or near transcription sites. Surprisingly, this retention mechanism requires the protein Rrp6p and the nuclear exosome, a large complex of exo nucleolytic enzymes(6,7). In exosome mutants, hypo- as well as hyperadenyla ted mRNAs are released and translated. These observations suggest that the exosome contributes to a checkpoint that monitors proper 3'-end formation o f mRNA.