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Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling
Splicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its ac...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149812/ https://www.ncbi.nlm.nih.gov/pubmed/34035302 http://dx.doi.org/10.1038/s41467-021-23459-4 |
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author | Yeh, Fu-Lung Chang, Shang-Lin Ahmed, Golam Rizvee Liu, Hsin-I Tung, Luh Yeh, Chung-Shu Lanier, Leah Stands Maeder, Corina Lin, Che-Min Tsai, Shu-Chun Hsiao, Wan-Yi Chang, Wei-Hau Chang, Tien-Hsien |
author_facet | Yeh, Fu-Lung Chang, Shang-Lin Ahmed, Golam Rizvee Liu, Hsin-I Tung, Luh Yeh, Chung-Shu Lanier, Leah Stands Maeder, Corina Lin, Che-Min Tsai, Shu-Chun Hsiao, Wan-Yi Chang, Wei-Hau Chang, Tien-Hsien |
author_sort | Yeh, Fu-Lung |
collection | PubMed |
description | Splicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its active site. Each of these major changes requires a dedicated DExD/H-box ATPase, but how these enzymes are activated remain obscure. Here we show that Prp28, a yeast DEAD-box ATPase, transiently interacts with the conserved 5′ splice-site (5′SS) GU dinucleotide and makes splicing-dependent contacts with the U1 snRNP protein U1C, and U4/U6.U5 tri-snRNP proteins, Prp8, Brr2, and Snu114. We further show that Prp28’s ATPase activity is potentiated by the phosphorylated Npl3, but not the unphosphorylated Npl3, thus suggesting a strategy for regulating DExD/H-box ATPases. We propose that Npl3 is a functional counterpart of the metazoan-specific Prp28 N-terminal region, which can be phosphorylated and serves as an anchor to human spliceosome. |
format | Online Article Text |
id | pubmed-8149812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-81498122021-06-11 Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling Yeh, Fu-Lung Chang, Shang-Lin Ahmed, Golam Rizvee Liu, Hsin-I Tung, Luh Yeh, Chung-Shu Lanier, Leah Stands Maeder, Corina Lin, Che-Min Tsai, Shu-Chun Hsiao, Wan-Yi Chang, Wei-Hau Chang, Tien-Hsien Nat Commun Article Splicing, a key step in the eukaryotic gene-expression pathway, converts precursor messenger RNA (pre-mRNA) into mRNA by excising introns and ligating exons. This task is accomplished by the spliceosome, a macromolecular machine that must undergo sequential conformational changes to establish its active site. Each of these major changes requires a dedicated DExD/H-box ATPase, but how these enzymes are activated remain obscure. Here we show that Prp28, a yeast DEAD-box ATPase, transiently interacts with the conserved 5′ splice-site (5′SS) GU dinucleotide and makes splicing-dependent contacts with the U1 snRNP protein U1C, and U4/U6.U5 tri-snRNP proteins, Prp8, Brr2, and Snu114. We further show that Prp28’s ATPase activity is potentiated by the phosphorylated Npl3, but not the unphosphorylated Npl3, thus suggesting a strategy for regulating DExD/H-box ATPases. We propose that Npl3 is a functional counterpart of the metazoan-specific Prp28 N-terminal region, which can be phosphorylated and serves as an anchor to human spliceosome. Nature Publishing Group UK 2021-05-25 /pmc/articles/PMC8149812/ /pubmed/34035302 http://dx.doi.org/10.1038/s41467-021-23459-4 Text en © The Author(s) 2021 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 Yeh, Fu-Lung Chang, Shang-Lin Ahmed, Golam Rizvee Liu, Hsin-I Tung, Luh Yeh, Chung-Shu Lanier, Leah Stands Maeder, Corina Lin, Che-Min Tsai, Shu-Chun Hsiao, Wan-Yi Chang, Wei-Hau Chang, Tien-Hsien Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title | Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title_full | Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title_fullStr | Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title_full_unstemmed | Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title_short | Activation of Prp28 ATPase by phosphorylated Npl3 at a critical step of spliceosome remodeling |
title_sort | activation of prp28 atpase by phosphorylated npl3 at a critical step of spliceosome remodeling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149812/ https://www.ncbi.nlm.nih.gov/pubmed/34035302 http://dx.doi.org/10.1038/s41467-021-23459-4 |
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