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Antagonistic actions of two human Pan3 isoforms on global mRNA turnover

Deadenylation is a fundamental process that regulates eukaryotic gene expression. Mammalian deadenylation exhibits biphasic kinetics, with the Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes mediating the first and second phase, respectively; however, the significance of the biphasic nature of deadeny...

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Autores principales: Chen, Chyi-Ying A., Zhang, Yueqiang, Xiang, Yu, Han, Leng, Shyu, Ann-Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558910/
https://www.ncbi.nlm.nih.gov/pubmed/28559491
http://dx.doi.org/10.1261/rna.061556.117
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author Chen, Chyi-Ying A.
Zhang, Yueqiang
Xiang, Yu
Han, Leng
Shyu, Ann-Bin
author_facet Chen, Chyi-Ying A.
Zhang, Yueqiang
Xiang, Yu
Han, Leng
Shyu, Ann-Bin
author_sort Chen, Chyi-Ying A.
collection PubMed
description Deadenylation is a fundamental process that regulates eukaryotic gene expression. Mammalian deadenylation exhibits biphasic kinetics, with the Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes mediating the first and second phase, respectively; however, the significance of the biphasic nature of deadenylation in mRNA turnover remains unclear. In this study, we discovered that two distinct isoforms of human Pan3 display opposing properties necessary for coordinating the two phases of deadenylation. The shorter isoform (Pan3S) interacts more strongly with PABP than the longer isoform (Pan3L) does. Pan2 deadenylase activity is enhanced by Pan3S but suppressed by Pan3L. Knocking down individual Pan3 isoforms has opposing effects on the global poly(A) tail length profile, P-body formation, and different mRNA decay pathways. Transcriptome-wide analysis of Pan3 knockdown effects on mRNA turnover shows that depleting either Pan3 isoform causes profound and extensive changes in mRNA stability globally. These results reveal a new fundamental step governing mammalian mRNA metabolism. We propose that the first phase of deadenylation, coordinated through the interplay among the two Pan3 isoforms, Pan2, and PABP, represents a cytoplasmic mRNA maturation step important for proper mRNA turnover.
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spelling pubmed-55589102018-09-01 Antagonistic actions of two human Pan3 isoforms on global mRNA turnover Chen, Chyi-Ying A. Zhang, Yueqiang Xiang, Yu Han, Leng Shyu, Ann-Bin RNA Article Deadenylation is a fundamental process that regulates eukaryotic gene expression. Mammalian deadenylation exhibits biphasic kinetics, with the Pan2–Pan3 and Ccr4–Caf1 deadenylase complexes mediating the first and second phase, respectively; however, the significance of the biphasic nature of deadenylation in mRNA turnover remains unclear. In this study, we discovered that two distinct isoforms of human Pan3 display opposing properties necessary for coordinating the two phases of deadenylation. The shorter isoform (Pan3S) interacts more strongly with PABP than the longer isoform (Pan3L) does. Pan2 deadenylase activity is enhanced by Pan3S but suppressed by Pan3L. Knocking down individual Pan3 isoforms has opposing effects on the global poly(A) tail length profile, P-body formation, and different mRNA decay pathways. Transcriptome-wide analysis of Pan3 knockdown effects on mRNA turnover shows that depleting either Pan3 isoform causes profound and extensive changes in mRNA stability globally. These results reveal a new fundamental step governing mammalian mRNA metabolism. We propose that the first phase of deadenylation, coordinated through the interplay among the two Pan3 isoforms, Pan2, and PABP, represents a cytoplasmic mRNA maturation step important for proper mRNA turnover. Cold Spring Harbor Laboratory Press 2017-09 /pmc/articles/PMC5558910/ /pubmed/28559491 http://dx.doi.org/10.1261/rna.061556.117 Text en © 2017 Chen et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by the RNA Society for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Chen, Chyi-Ying A.
Zhang, Yueqiang
Xiang, Yu
Han, Leng
Shyu, Ann-Bin
Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title_full Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title_fullStr Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title_full_unstemmed Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title_short Antagonistic actions of two human Pan3 isoforms on global mRNA turnover
title_sort antagonistic actions of two human pan3 isoforms on global mrna turnover
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558910/
https://www.ncbi.nlm.nih.gov/pubmed/28559491
http://dx.doi.org/10.1261/rna.061556.117
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