Molecular basis for METTL9-mediated N1-histidine methylation

Wang, Xiaoyang; Xie, Huabin; Guo, Qiong; Cao, Dan; Ru, Wenwen; Zhao, Shidong; Zhu, Zhongliang; Zhang, Jiahai; Pan, Wen; Yao, Xuebiao; Xu, Chao

doi:10.1038/s41421-023-00548-w

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Several proteinogenic amino acids possess nucleophilic functional groups in their side chains ( Figure 2 and S1 ). Some of these have been shown to be post-translationally modified by acylations (37) and methylations (38, 39). The chemical probing reagents 1M7 (1-methyl-7-nitro-isatoic anhydride) and DMS (dimethyl sulfate) are capable of reacting with side chain nucleophiles in a similar manner.…”

Section: Resultsmentioning

confidence: 99%

RNA Chemical Probing Reagents and Protein Amino Acids: a Double-Edged Sword

Fallon,

Klingler,

Cohn

et al. 2024

Preprint

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RNA chemical probing experiments are a broadly used method for revealing the structure of RNA, as well as for identifying protein binding sites. This is beneficial for expanding our understanding of biological processes governed by protein-RNA complex interactions, as well as facilitating the identification of complex inhibiting molecules. The reagents commonly used in chemical probing experiments are highly reactive, methylating or acylating atoms of flexible RNA nucleotides. The highly reactive nature of the chemical probes means that they can also react with nucleophilic amino acid side chains, and subsequently affect protein-RNA binding events. We combine MD simulations, MALDI-MS, and NMR experiments to show that commonly used RNA chemical probes react with protein amino acids, and demonstrate that this effect alters protein-RNA binding interactions through binding shift assays. We discuss the implications of this phenomenon in elucidating protein-RNA interactions, and also demonstrate this as a useful means for identifying surface-exposed protein residues, omitting the need for extensive mutagenesis experiments that are critical for RNA interactions.

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Section: Resultsmentioning

confidence: 99%

RNA Chemical Probing Reagents and Protein Amino Acids: a Double-Edged Sword

Fallon,

Klingler,

Cohn

et al. 2024

Preprint

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A novel N6-Deoxyadenine methyltransferase METL-9 modulates C. elegans immunity via dichotomous mechanisms

Xue

Peng

et al. 2023

Cell Res

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N6-Methyldeoxyadenine (6mA) has been rediscovered as a DNA modification with potential biological function in metazoans. However, the physiological function and regulatory mechanisms regarding the establishment, maintenance and removal of 6mA in eukaryotes are still poorly understood. Here we show that genomic 6mA levels change in response to pathogenic infection in Caenorhabditis elegans (C. elegans). We further identify METL-9 as the methyltransferase that catalyzes DNA 6mA modifications upon pathogen infection. Deficiency of METL-9 impairs the induction of innate immune response genes and renders the animals more susceptible to pathogen infection. Interestingly, METL-9 functions through both 6mA-dependent and -independent mechanisms to transcriptionally regulate innate immunity. Our findings reveal that 6mA is a functional DNA modification in immunomodulation in C. elegans.

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Molecular basis for METTL9-mediated N1-histidine methylation

Cited by 2 publications

References 16 publications

RNA Chemical Probing Reagents and Protein Amino Acids: a Double-Edged Sword

RNA Chemical Probing Reagents and Protein Amino Acids: a Double-Edged Sword

A novel N6-Deoxyadenine methyltransferase METL-9 modulates C. elegans immunity via dichotomous mechanisms

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