Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome

Proc Natl Acad Sci U S A. 2021 Apr 6;118(14):e2024846118. doi: 10.1073/pnas.2024846118.


Quality control requires discrimination between functional and aberrant species to selectively target aberrant substrates for destruction. Nuclear RNA quality control in Saccharomyces cerevisiae includes the TRAMP complex that marks RNA for decay via polyadenylation followed by helicase-dependent 3' to 5' degradation by the RNA exosome. Using reconstitution biochemistry, we show that polyadenylation and helicase activities of TRAMP cooperate with processive and distributive exoribonuclease activities of the nuclear RNA exosome to protect stable RNA from degradation while selectively targeting and degrading less stable RNA. Substrate discrimination is lost when the distributive exoribonuclease activity of Rrp6 is inactivated, leading to degradation of stable and unstable RNA species. These data support a proofreading mechanism in which deadenylation by Rrp6 competes with Mtr4-dependent degradation to protect stable RNA while selectively targeting and degrading unstable RNA.

Keywords: RNA; RNA decay; TRAMP; exosome; quality control.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Exosome Multienzyme Ribonuclease Complex / genetics
  • Exosome Multienzyme Ribonuclease Complex / metabolism*
  • Exosomes / genetics
  • Exosomes / metabolism
  • Polyadenylation
  • RNA Stability*
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • Saccharomyces cerevisiae Proteins
  • Exosome Multienzyme Ribonuclease Complex
  • RRP6 protein, S cerevisiae
  • MTR4 protein, S cerevisiae
  • DEAD-box RNA Helicases