Global view on the metabolism of RNA poly(A) tails in yeast Saccharomyces cerevisiae

The polyadenosine tail (poly[A]-tail) is a universal modification of eukaryotic messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). In budding yeast, mRNA poly(A)-tails are produced by Pap1 to enhance export and translation, whereas the Trf4/5-mediated polyadenylation of ncRNAs facilitates degradation. Using direct RNA sequencing, we deciphered the extent of poly(A)-tail dynamics in yeast strains that were defective of all relevant exonucleases, deadenylases, and poly(A)-polymerases. The newly synthesized mRNA poly(A)-tails with a length of 50-70 adenosines were deadenylated to a steady-state length of 40 adenosines. We found that poly(A)-tails underwent exosome-nuclear trimming and PAN2/3[or CCR4-NOT cytoplasmic deadenylation. Trf4/5 can adenylate mRNAs, although Trf5 mainly enhances mRNA poly(A)-tail trimming by the exosome. PAN2/3 and CCR4-NOT can differ in specificity with a large pool of non-overlapping substrates. Collectively, exonucleolysis controls the poly(A)-tail length of at least two-thirds of the coding transcriptome, which is tailored to a given mRNA partially independently of translation rate and in response to growth conditions.