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

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′...

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Autores principales: Das, Mom, Zattas, Dimitrios, Zinder, John C., Wasmuth, Elizabeth V., Henri, Julien, Lima, Christopher D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040639/
https://www.ncbi.nlm.nih.gov/pubmed/33782132
http://dx.doi.org/10.1073/pnas.2024846118
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author Das, Mom
Zattas, Dimitrios
Zinder, John C.
Wasmuth, Elizabeth V.
Henri, Julien
Lima, Christopher D.
author_facet Das, Mom
Zattas, Dimitrios
Zinder, John C.
Wasmuth, Elizabeth V.
Henri, Julien
Lima, Christopher D.
author_sort Das, Mom
collection PubMed
description 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.
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spelling pubmed-80406392021-04-20 Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome Das, Mom Zattas, Dimitrios Zinder, John C. Wasmuth, Elizabeth V. Henri, Julien Lima, Christopher D. Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2021-04-06 2021-03-29 /pmc/articles/PMC8040639/ /pubmed/33782132 http://dx.doi.org/10.1073/pnas.2024846118 Text en Copyright © 2021 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biological Sciences
Das, Mom
Zattas, Dimitrios
Zinder, John C.
Wasmuth, Elizabeth V.
Henri, Julien
Lima, Christopher D.
Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title_full Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title_fullStr Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title_full_unstemmed Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title_short Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome
title_sort substrate discrimination and quality control require each catalytic activity of tramp and the nuclear rna exosome
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040639/
https://www.ncbi.nlm.nih.gov/pubmed/33782132
http://dx.doi.org/10.1073/pnas.2024846118
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