REVIEW: The Functions of N⁶-Methyladenosine in Nuclear RNAs

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Nadezhda A. Zhigalova¹, Katerina Yu. Oleynikova¹, Alexey S. Ruzov¹, and Alexander S. Ermakov^1,2,a*

¹Institute of Bioengineering, Research Center of Biotechnology, Russian Academy of Sciences, 119071 Moscow, Russia

²Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

Received July 23, 2023; Revised November 24, 2023; Accepted November 24, 2023

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N⁶-methyladenosine (m⁶A) is one of the most common modifications in both eukaryotic and prokaryotic mRNAs. It has been experimentally confirmed that m⁶A methylation is involved in the regulation of stability and translation of various mRNAs. Until recently, the majority of m⁶A-related studies have been focused on the cytoplasmic functions of this modification. Here, we review new data on the role of m⁶A in several key biological processes taking place in the cell nucleus, such as transcription, chromatin organization, splicing, nuclear-cytoplasmic transport, and R-loop metabolism. Based on analysis of these data, we suggest that m⁶A methylation of nuclear RNAs is another level of gene expression regulation which, together with DNA methylation and histone modifications, controls chromatin structure and functioning in various biological contexts.

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KEY WORDS: RNA modifications, N⁶-methyladenosine (m⁶A), methyltransferases METTL3 and METTL14, demethylases FTO and ALKBH5, m⁶A-binding proteins of the YTHDF and YTHDC families, chromatin, R-loops

DOI: 10.1134/S0006297924010103

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