摘要
N6-methyladenosine(m^(6)A)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 m^(6)A 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 m^(6)A methylation by mapping the quantitative trait loci of m^(6)A(m^(6)A-QTLs),thereby building up the regulatory circuits linking genetic variants,m^(6)A,and human complex traits.Here,we review the recent discoveries concerning the genetic regulatory maps of m^(6)A,describing the methodological and technical details of m^(6)A-QTL identification,and introducing the key findings of the cis-and trans-acting drivers of m^(6)A.We further delve into the tissue-and ethnicity-specificity of m^(6)A-QTL,the association with other molecular phenotypes in light of genetic regulation,the regulators underlying m^(6)A genetics,and importantly,the functional roles of m^(6)A in mediating human complex diseases.Lastly,we discuss potential research avenues that can accelerate the translation of m^(6)A genetics studies toward the development of therapies for human genetic diseases.
基金
supported by the National Natural Science Foundation of China(32370609 and 92353301 to X.X.)
funding from Liangzhu Laboratory at Zhejiang University and the State Key Laboratory of Transvascular Implantation Devices at Zhejiang University.
