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.
Highlights
Quality control requires discrimination between functional and aberrant species to selectively target aberrant substrates for destruction
Our study supports a model for substrate discrimination and RNA quality control that relies on each of the catalytic activities of TRAMP and the nuclear exosome to selectively degrade less stable substrates while protecting more stable species from degradation (Fig. 7)
Our in vitro data suggest that polyadenylation is required for TRAMP-mediated Dis3-dependent decay of unmodified tRNA by the nuclear RNA exosome
Summary
Quality control requires discrimination between functional and aberrant species to selectively target aberrant substrates for destruction. Substrate discrimination is lost when the distributive exoribonuclease activity of Rrp is inactivated, leading to degradation of stable and unstable RNA species These data support a proofreading mechanism in which deadenylation by Rrp competes with Mtr4dependent degradation to protect stable RNA while selectively targeting and degrading unstable RNA. Mtr is a core subunit of several complexes that engage RNA substrates prior to degradation Among these is TRAMP, a complex conserved across eukaryotic evolution; and PAXT, which appear conserved in metazoans; and MTREC, a complex discovered in fission yeast that includes the Mtr4-like helicase Mtl1 [5, 7]
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