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Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2
CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820811/ https://www.ncbi.nlm.nih.gov/pubmed/35129087 http://dx.doi.org/10.1080/15476286.2021.2021676 |
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author | Suzuki, Toru Hoshina, Miyuki Nishijima, Saori Hoshina, Naosuke Kikuguchi, Chisato Tomohiro, Takumi Fukao, Akira Fujiwara, Toshinobu Yamamoto, Tadashi |
author_facet | Suzuki, Toru Hoshina, Miyuki Nishijima, Saori Hoshina, Naosuke Kikuguchi, Chisato Tomohiro, Takumi Fukao, Akira Fujiwara, Toshinobu Yamamoto, Tadashi |
author_sort | Suzuki, Toru |
collection | PubMed |
description | CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by osmotic stress in CNOT2-depleted cells, indicating that CNOT2 is responsible for stress resistance of cells. Although wild-type (WT) and non-phosphorylatable CNOT2 mutants reverse this sensitivity, a phosphomimetic form of CNOT2, in which serine at the phosphorylation site is replaced with glutamate, does not have this function. We also show that mRNAs have elongated poly(A) tails in CNOT2-depleted cells and that introduction of CNOT2 WT or a non-phosphorylatable mutant, but not phosphomimetic CNOT2, renders their poly(A) tail lengths comparable to those in control HeLa cells. Consistent with this, the CCR4-NOT complex containing phosphomimetic CNOT2 exhibits less deadenylase activity than that containing CNOT2 WT. These data suggest that CCR4-NOT complex deadenylase activity is regulated by post-translational modification, yielding dynamic control of mRNA deadenylation. |
format | Online Article Text |
id | pubmed-8820811 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-88208112022-02-08 Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 Suzuki, Toru Hoshina, Miyuki Nishijima, Saori Hoshina, Naosuke Kikuguchi, Chisato Tomohiro, Takumi Fukao, Akira Fujiwara, Toshinobu Yamamoto, Tadashi RNA Biol Research Paper CCR4-NOT complex-mediated mRNA deadenylation serves critical functions in multiple biological processes, yet how this activity is regulated is not fully understood. Here, we show that osmotic stress induces MAPKAPK-2 (MK2)-mediated phosphorylation of CNOT2. Programmed cell death is greatly enhanced by osmotic stress in CNOT2-depleted cells, indicating that CNOT2 is responsible for stress resistance of cells. Although wild-type (WT) and non-phosphorylatable CNOT2 mutants reverse this sensitivity, a phosphomimetic form of CNOT2, in which serine at the phosphorylation site is replaced with glutamate, does not have this function. We also show that mRNAs have elongated poly(A) tails in CNOT2-depleted cells and that introduction of CNOT2 WT or a non-phosphorylatable mutant, but not phosphomimetic CNOT2, renders their poly(A) tail lengths comparable to those in control HeLa cells. Consistent with this, the CCR4-NOT complex containing phosphomimetic CNOT2 exhibits less deadenylase activity than that containing CNOT2 WT. These data suggest that CCR4-NOT complex deadenylase activity is regulated by post-translational modification, yielding dynamic control of mRNA deadenylation. Taylor & Francis 2022-02-06 /pmc/articles/PMC8820811/ /pubmed/35129087 http://dx.doi.org/10.1080/15476286.2021.2021676 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Suzuki, Toru Hoshina, Miyuki Nishijima, Saori Hoshina, Naosuke Kikuguchi, Chisato Tomohiro, Takumi Fukao, Akira Fujiwara, Toshinobu Yamamoto, Tadashi Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title | Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title_full | Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title_fullStr | Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title_full_unstemmed | Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title_short | Regulation of CCR4-NOT complex deadenylase activity and cellular responses by MK2-dependent phosphorylation of CNOT2 |
title_sort | regulation of ccr4-not complex deadenylase activity and cellular responses by mk2-dependent phosphorylation of cnot2 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820811/ https://www.ncbi.nlm.nih.gov/pubmed/35129087 http://dx.doi.org/10.1080/15476286.2021.2021676 |
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