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Genetic regulation of m6A RNA methylation and its contribution in human complex diseases

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Abstract

N6-methyladenosine (m6A) has been established as the most prevalent chemical modification in message RNA (mRNA), playing an essential role in determining the fate of RNA molecules. Dysregulation of m6A has been revealed to lead to abnormal physiological conditions and cause various types of human diseases. Recent studies have delineated the genetic regulatory maps for m6A methylation by mapping the quantitative trait loci of m6A (m6A-QTLs), thereby building up the regulatory circuits linking genetic variants, m6A, and human complex traits. Here, we review the recent discoveries concerning the genetic regulatory maps of m6A, describing the methodological and technical details of m6A-QTL identification, and introducing the key findings of the cis- and trans-acting drivers of m6A. We further delve into the tissue- and ethnicity-specificity of m6A-QTL, the association with other molecular phenotypes in light of genetic regulation, the regulators underlying m6A genetics, and importantly, the functional roles of m6A in mediating human complex diseases. Lastly, we discuss potential research avenues that can accelerate the translation of m6A genetics studies toward the development of therapies for human genetic diseases.

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Acknowledgement

We thank the members of the Xiong Lab for the discussion. This work was supported by the National Natural Science Foundation of China (32370609 and 92353301 to X.X.), and funding from Liangzhu Laboratory at Zhejiang University and the State Key Laboratory of Transvascular Implantation Devices at Zhejiang University.

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Authors and Affiliations

  1. The Second Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou, 311121, China

    Kexuan Chen, Jiuhong Nan & Xushen Xiong

  2. State Key Laboratory of Transvascular Implantation Devices, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 311121, China

    Kexuan Chen, Jiuhong Nan & Xushen Xiong

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  1. Kexuan Chen
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  2. Jiuhong Nan
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  3. Xushen Xiong
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Correspondence to Xushen Xiong.

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Chen, K., Nan, J. & Xiong, X. Genetic regulation of m6A RNA methylation and its contribution in human complex diseases. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-024-2609-8

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  • DOI: https://doi.org/10.1007/s11427-024-2609-8

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