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

Mom Das, Dimitrios Zattas, John C. Zinder, Elizabeth V. Wasmuth, Julien Henri, Christopher D. Lima

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere2024846118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number14
DOIs
StatePublished - Apr 6 2021
Externally publishedYes

Keywords

  • Exosome
  • Quality control
  • RNA
  • RNA decay
  • TRAMP

ASJC Scopus subject areas

  • General

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