The 18SrRNAm(6)A methyltransferaseMETTL5 promotes mouse embryonic stem cell differentiation

Xing, Ming1; Liu, Qi2; Mao, Cong1; Zeng, Hanyi1; Zhang, Xin1; Zhao, Shuqin1; Chen, Li1; Liu, Mingxi1; Shen, Bin1; Guo, Xuejiang1; Ma, Honghui3; Chen, Hao4; Zhang, Jun1

2020-08-11

10.15252/embr.201949863

EMBO REPORTS   影响因子和分区

1469-221X

1469-3178

RNAmodifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N-6-methyladenosine (m(6)A) on messengerRNA(mRNA) plays critical roles in cell fate determination and development. m(6)A mark also resides in the decoding center of 18S ribosomalRNA(rRNA); however, the biological function of m(6)A on 18SrRNAis still poorly understood. Here, we report that methyltransferase-like 5 (METTL5) methylates 18SrRNAbothin vivoandin vitro, which is consistent with previous reports. Deletion ofMettl5causes a dramatic differentiation defect in mouse embryonic stem cells (mESCs). Mechanistically, the m(6)A deposited byMETTL5 is involved in regulating the efficient translation of F-box andWDrepeat domain-containing 7 (FBXW7), a key regulator of cell differentiation. Deficiency ofMETTL5 reducesFBXW7 levels and leads to the accumulation of its substrate c-MYC, thereby delaying the onset ofmESCdifferentiation. Our study uncovers an important role ofMETTL5-mediated 18S m(6)A inmESCdifferentiation through translation regulation and provides new insight into the functional significance ofrRNAm(6)A.

FBXW7 m(6)A mESCdifferentiation mRNAtranslation rRNA

SCI

英语

通讯

National Key R&D program of China[2017YFC1001302][2016YFA0503300][2016YFA0500902] ; National Natural Science Foundation of China[31871445][31971330] ; Science and Technology Development Fund of Nanjing Medical University-General Project[2017NJMU019] ; Southern University of Science and Technology[Y01411801][Y01416116]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:000558207300001

WILEY

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing, Peoples R China
2.Chinese Acad Forestry, Res Inst Forestry, State Key Lab Tree Genet & Breeding, Beijing, Peoples R China
3.Tongji Univ, East Hosp, Key Lab Arrhythmias, Sch Med,Minist Educ China, Shanghai, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China

Xing, Ming,Liu, Qi,Mao, Cong,et al. The 18SrRNAm(6)A methyltransferaseMETTL5 promotes mouse embryonic stem cell differentiation[J]. EMBO REPORTS,2020.

Xing, Ming.,Liu, Qi.,Mao, Cong.,Zeng, Hanyi.,Zhang, Xin.,...&Zhang, Jun.(2020).The 18SrRNAm(6)A methyltransferaseMETTL5 promotes mouse embryonic stem cell differentiation.EMBO REPORTS.

Xing, Ming,et al."The 18SrRNAm(6)A methyltransferaseMETTL5 promotes mouse embryonic stem cell differentiation".EMBO REPORTS (2020).