Highly sequence-specific, timing-controllable m6A demethylation by modulating RNA-binding affinity of m6A erasers

Kenko Otonari; Yuri Asami; Kosuke Ogata; Yasushi Ishihama; Shiroh Futaki; Miki Imanishi

doi:10.1039/d4cc04070h

Highly sequence-specific, timing-controllable m⁶A demethylation by modulating RNA-binding affinity of m⁶A erasers

Chem Commun (Camb). 2024 Dec 17;61(1):69-72. doi: 10.1039/d4cc04070h.

Authors

Kenko Otonari¹, Yuri Asami¹, Kosuke Ogata², Yasushi Ishihama^{3

2}, Shiroh Futaki¹, Miki Imanishi¹

Affiliations

¹ Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. [email protected].
² National Institute of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka 567-0085, Japan.
³ Graduate School of Pharmaceutical Science, Kyoto University, Kyoto 606-8501, Japan.

PMID: 39499124
DOI: 10.1039/d4cc04070h

Abstract

Recent advancements in tools using programmable RNA binding proteins and m⁶A-erasers enable sequence-selective and timing-controllable m⁶A demethylation. However, off-target effects are still a concern. This study addresses the problem by reducing the RNA-binding ability of m⁶A-erasers. The modulated m⁶A-erasers achieved sequence-specific and timing-controllable m⁶A demethylation with minimal off-target activity.

MeSH terms

Adenosine / chemistry
Adenosine / metabolism
Demethylation*
Humans
Methyltransferases / chemistry
Methyltransferases / metabolism
Protein Binding
RNA* / chemistry
RNA* / metabolism
RNA-Binding Proteins* / chemistry
RNA-Binding Proteins* / metabolism

Substances

RNA-Binding Proteins
RNA
Adenosine
Methyltransferases