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Metabolic labeling based methylome profiling enables functional dissection of histidine methylation in C3H1 zinc fingers

Keyun Wang, Li Zhang, Sirui Zhang, Ye Liu, Jiawei Mao, Zhen Liu, Lin Xu, Kejia Li, Jianshu Wang, Yanni Ma, Jiayi Wang, Haitao Li, Zefeng Wang (), Guohui Li (), Hong Cheng () and Mingliang Ye ()
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Keyun Wang: Chinese Academy of Sciences
Li Zhang: Chinese Academy of Sciences, University of Chinese Academy of Sciences
Sirui Zhang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Ye Liu: Chinese Academy of Sciences
Jiawei Mao: Chinese Academy of Sciences
Zhen Liu: Chinese Academy of Sciences
Lin Xu: Chinese Academy of Sciences, University of Chinese Academy of Sciences
Kejia Li: Chinese Academy of Sciences
Jianshu Wang: Chinese Academy of Sciences, University of Chinese Academy of Sciences
Yanni Ma: Chinese Academy of Sciences
Jiayi Wang: Chinese Academy of Sciences
Haitao Li: Tsinghua University
Zefeng Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Guohui Li: Chinese Academy of Sciences
Hong Cheng: Chinese Academy of Sciences, University of Chinese Academy of Sciences
Mingliang Ye: Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.

Date: 2024
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DOI: 10.1038/s41467-024-51979-2

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