Genetic regulation of m^(6)A RNA methylation and its contribution in human complex diseases  

作　　者：Kexuan Chen Jiuhong Nan Xushen Xiong 

机构地区：[1]The Second Affiliated Hospital&Liangzhu Laboratory,Zhejiang University School of Medicine,Hangzhou 311121,China [2]State Key Laboratory of Transvascular Implantation Devices,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 311121,China

出　　处：《Science China(Life Sciences)》2024年第8期1591-1600,共10页中国科学（生命科学英文版）

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.

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.

关 键 词：m^(6)A disease genetics m^(6)A-QTL GWAS 

分 类 号：R394[医药卫生—医学遗传学]