K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis

N6-methyladenosine (m(6)A) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two m(6)A demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7. K235 acetylati...

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Autores principales: Zhang, Xiao-Lan, Chen, Xin-Hui, Xu, Binwu, Chen, Min, Zhu, Song, Meng, Nan, Wang, Ji-Zhong, Zhu, Huifang, Chen, De, Liu, Jin-Bao, Yan, Guang-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300122/
https://www.ncbi.nlm.nih.gov/pubmed/37369679
http://dx.doi.org/10.1038/s41467-023-39414-4
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author Zhang, Xiao-Lan
Chen, Xin-Hui
Xu, Binwu
Chen, Min
Zhu, Song
Meng, Nan
Wang, Ji-Zhong
Zhu, Huifang
Chen, De
Liu, Jin-Bao
Yan, Guang-Rong
author_facet Zhang, Xiao-Lan
Chen, Xin-Hui
Xu, Binwu
Chen, Min
Zhu, Song
Meng, Nan
Wang, Ji-Zhong
Zhu, Huifang
Chen, De
Liu, Jin-Bao
Yan, Guang-Rong
author_sort Zhang, Xiao-Lan
collection PubMed
description N6-methyladenosine (m(6)A) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two m(6)A demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7. K235 acetylation strengthens the m(6)A demethylation activity of ALKBH5 by increasing its recognition of m(6)A on mRNA. RNA-binding protein paraspeckle component 1 (PSCP1) is a regulatory subunit of ALKBH5 and preferentially interacts with K235-acetylated ALKBH5 to recruit and facilitate the recognition of m(6)A mRNA by ALKBH5, thereby promoting m(6)A erasure. Mitogenic signals promote ALKBH5 K235 acetylation. K235 acetylation of ALKBH5 is upregulated in cancers and promotes tumorigenesis. Thus, our findings reveal that the m(6)A demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the m(6)A demethylase activity and oncogenic roles of ALKBH5.
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spelling pubmed-103001222023-06-29 K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis Zhang, Xiao-Lan Chen, Xin-Hui Xu, Binwu Chen, Min Zhu, Song Meng, Nan Wang, Ji-Zhong Zhu, Huifang Chen, De Liu, Jin-Bao Yan, Guang-Rong Nat Commun Article N6-methyladenosine (m(6)A) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two m(6)A demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7. K235 acetylation strengthens the m(6)A demethylation activity of ALKBH5 by increasing its recognition of m(6)A on mRNA. RNA-binding protein paraspeckle component 1 (PSCP1) is a regulatory subunit of ALKBH5 and preferentially interacts with K235-acetylated ALKBH5 to recruit and facilitate the recognition of m(6)A mRNA by ALKBH5, thereby promoting m(6)A erasure. Mitogenic signals promote ALKBH5 K235 acetylation. K235 acetylation of ALKBH5 is upregulated in cancers and promotes tumorigenesis. Thus, our findings reveal that the m(6)A demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the m(6)A demethylase activity and oncogenic roles of ALKBH5. Nature Publishing Group UK 2023-06-27 /pmc/articles/PMC10300122/ /pubmed/37369679 http://dx.doi.org/10.1038/s41467-023-39414-4 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
Zhang, Xiao-Lan
Chen, Xin-Hui
Xu, Binwu
Chen, Min
Zhu, Song
Meng, Nan
Wang, Ji-Zhong
Zhu, Huifang
Chen, De
Liu, Jin-Bao
Yan, Guang-Rong
K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title_full K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title_fullStr K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title_full_unstemmed K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title_short K235 acetylation couples with PSPC1 to regulate the m(6)A demethylation activity of ALKBH5 and tumorigenesis
title_sort k235 acetylation couples with pspc1 to regulate the m(6)a demethylation activity of alkbh5 and tumorigenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10300122/
https://www.ncbi.nlm.nih.gov/pubmed/37369679
http://dx.doi.org/10.1038/s41467-023-39414-4
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