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

Read more

Summary

Introduction

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]

Methods
Results
Conclusion

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.