Uridylation regulates mRNA decay directionality in fission yeast.

Abstract Cytoplasmic mRNA decay is effected by exonucleolytic degradation in in either the 5' to 3' or 3' to 5' direction. Pervasive terminal uridylation is implicated in mRNA degradation, however, despite its conservation throughout eucaryotes, its functional relevance for bulk mRNA turnover remains poorly understood. In this study, we employed genome-wide 3'-RACE technique to elucidate the role of uridylation in governing mRNA decay directionality. The observed widespread uridylation of shortened poly(A) tails promotes efficient 5' to 3' mRNA decay, ensuring timely and controlled mRNA degradation. Conversely, the inhibition of this uridylation process disrupts the delicate balance, leading to excessive deadenylation and enhanced 3' to 5' mRNA decay accompanied by oligouridylation of de-adenylated mRNAs. Strikingly we found that in fission yeast uridylation of poly(A) tails and oligouridylation of non-polyadenylated substrates are catalysed by different terminal uridyltransferases. Our study sheds new light on the intricate regulatory mechanisms underlying bulk mRNA turnover, emphasizing the role of uridylation in modulating mRNA decay pathways.