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Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex

The S. pombe orthologue of the human PAXT connection, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex that targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA...

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Autores principales: Soni, Komal, Sivadas, Anusree, Horvath, Attila, Dobrev, Nikolay, Hayashi, Rippei, Kiss, Leo, Simon, Bernd, Wild, Klemens, Sinning, Irmgard, Fischer, Tamás
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922296/
https://www.ncbi.nlm.nih.gov/pubmed/36774373
http://dx.doi.org/10.1038/s41467-023-36402-6
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author Soni, Komal
Sivadas, Anusree
Horvath, Attila
Dobrev, Nikolay
Hayashi, Rippei
Kiss, Leo
Simon, Bernd
Wild, Klemens
Sinning, Irmgard
Fischer, Tamás
author_facet Soni, Komal
Sivadas, Anusree
Horvath, Attila
Dobrev, Nikolay
Hayashi, Rippei
Kiss, Leo
Simon, Bernd
Wild, Klemens
Sinning, Irmgard
Fischer, Tamás
author_sort Soni, Komal
collection PubMed
description The S. pombe orthologue of the human PAXT connection, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex that targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA transcripts as part of the cleavage and polyadenylation factor (CPF/CPSF). In this study we identify and characterise the interaction between Pla1 and the MTREC complex core component Red1 and analyse the functional relevance of this interaction in vivo. Our crystal structure of the Pla1-Red1 complex shows that a 58-residue fragment in Red1 binds to the RNA recognition motif domain of Pla1 and tethers it to the MTREC complex. Structure-based Pla1-Red1 interaction mutations show that Pla1, as part of MTREC complex, hyper-adenylates CUTs for their efficient degradation. Interestingly, the Red1-Pla1 interaction is also required for the efficient assembly of the fission yeast facultative heterochromatic islands. Together, our data suggest a complex interplay between the RNA surveillance and 3’-end processing machineries.
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spelling pubmed-99222962023-02-13 Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex Soni, Komal Sivadas, Anusree Horvath, Attila Dobrev, Nikolay Hayashi, Rippei Kiss, Leo Simon, Bernd Wild, Klemens Sinning, Irmgard Fischer, Tamás Nat Commun Article The S. pombe orthologue of the human PAXT connection, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex that targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA transcripts as part of the cleavage and polyadenylation factor (CPF/CPSF). In this study we identify and characterise the interaction between Pla1 and the MTREC complex core component Red1 and analyse the functional relevance of this interaction in vivo. Our crystal structure of the Pla1-Red1 complex shows that a 58-residue fragment in Red1 binds to the RNA recognition motif domain of Pla1 and tethers it to the MTREC complex. Structure-based Pla1-Red1 interaction mutations show that Pla1, as part of MTREC complex, hyper-adenylates CUTs for their efficient degradation. Interestingly, the Red1-Pla1 interaction is also required for the efficient assembly of the fission yeast facultative heterochromatic islands. Together, our data suggest a complex interplay between the RNA surveillance and 3’-end processing machineries. Nature Publishing Group UK 2023-02-11 /pmc/articles/PMC9922296/ /pubmed/36774373 http://dx.doi.org/10.1038/s41467-023-36402-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Soni, Komal
Sivadas, Anusree
Horvath, Attila
Dobrev, Nikolay
Hayashi, Rippei
Kiss, Leo
Simon, Bernd
Wild, Klemens
Sinning, Irmgard
Fischer, Tamás
Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title_full Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title_fullStr Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title_full_unstemmed Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title_short Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
title_sort mechanistic insights into rna surveillance by the canonical poly(a) polymerase pla1 of the mtrec complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922296/
https://www.ncbi.nlm.nih.gov/pubmed/36774373
http://dx.doi.org/10.1038/s41467-023-36402-6
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