K235 Acetylation Couples with PSPC1 to Regulate the MA Demethylation Activity of ALKBH5 and Tumorigenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Jun 27

PMID 37369679

Authors

Xiao-Lan Zhang

Xin-Hui Chen

Binwu Xu

Min Chen

Song Zhu

Nan Meng

Ji-Zhong Wang

Huifang Zhu

De Chen

Jin-Bao Liu

Guang-Rong Yan

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (mA) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two mA 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 mA demethylation activity of ALKBH5 by increasing its recognition of mA 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 mA mRNA by ALKBH5, thereby promoting mA erasure. Mitogenic signals promote ALKBH5 K235 acetylation. K235 acetylation of ALKBH5 is upregulated in cancers and promotes tumorigenesis. Thus, our findings reveal that the mA demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the mA demethylase activity and oncogenic roles of ALKBH5.

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