RNA surveillance by uridylation-dependent RNA decay in Schizosaccharomyces pombe

Nucleic Acids Res. 2019 Apr 8;47(6):3045-3057. doi: 10.1093/nar/gkz043.


Uridylation-dependent RNA decay is a widespread eukaryotic pathway modulating RNA homeostasis. Terminal uridylyltransferases (Tutases) add untemplated uridyl residues to RNA 3'-ends, marking them for degradation by the U-specific exonuclease Dis3L2. In Schizosaccharomyces pombe, Cid1 uridylates a variety of RNAs. In this study, we investigate the prevalence and impact of uridylation-dependent RNA decay in S. pombe by transcriptionally profiling cid1 and dis3L2 deletion strains. We found that the exonuclease Dis3L2 represents a bottleneck in uridylation-dependent mRNA decay, whereas Cid1 plays a redundant role that can be complemented by other Tutases. Deletion of dis3L2 elicits a cellular stress response, upregulating transcription of genes involved in protein folding and degradation. Misfolded proteins accumulate in both deletion strains, yet only trigger a strong stress response in dis3L2 deficient cells. While a deletion of cid1 increases sensitivity to protein misfolding stress, a dis3L2 deletion showed no increased sensitivity or was even protective. We furthermore show that uridylyl- and adenylyltransferases cooperate to generate a 5'-NxAUUAAAA-3' RNA motif on dak2 mRNA. Our studies elucidate the role of uridylation-dependent RNA decay as part of a global mRNA surveillance, and we found that perturbation of this pathway leads to the accumulation of misfolded proteins and elicits cellular stress responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exoribonucleases / genetics
  • Exosome Multienzyme Ribonuclease Complex / genetics
  • Nucleotidyltransferases / genetics
  • RNA Nucleotidyltransferases / genetics*
  • RNA Stability / genetics*
  • RNA, Fungal / genetics
  • RNA, Messenger / genetics
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins / genetics*
  • Uridine / genetics


  • RNA, Fungal
  • RNA, Messenger
  • Schizosaccharomyces pombe Proteins
  • Nucleotidyltransferases
  • RNA Nucleotidyltransferases
  • UTP-RNA uridylyltransferase
  • Cid1 protein, S pombe
  • Exoribonucleases
  • Exosome Multienzyme Ribonuclease Complex
  • dis3 protein, S pombe
  • Uridine