The 18S rRNA m 6 A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation

RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N -methyladenosine (m A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m A mark also resides in the decoding center of 18S ribosomal RNA (rRNA);...

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Bibliographic Details
Published inEMBO reports Vol. 21; no. 10; p. e49863
Main Authors Xing, Ming, Liu, Qi, Mao, Cong, Zeng, Hanyi, Zhang, Xin, Zhao, Shuqin, Chen, Li, Liu, Mingxi, Shen, Bin, Guo, Xuejiang, Ma, Honghui, Chen, Hao, Zhang, Jun
Format Journal Article
LanguageEnglish
Published England 05.10.2020
Subjects
Animals
Cell Differentiation - genetics
Methyltransferases - genetics
Mice
Mouse Embryonic Stem Cells
RNA, Messenger
RNA, Ribosomal, 18S - genetics
mRNA translation
FBXW7
mESC differentiation
rRNA
m6A
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Summary:RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N -methyladenosine (m A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m A mark also resides in the decoding center of 18S ribosomal RNA (rRNA); however, the biological function of m A on 18S rRNA is still poorly understood. Here, we report that methyltransferase-like 5 (METTL5) methylates 18S rRNA both in vivo and in vitro, which is consistent with previous reports. Deletion of Mettl5 causes a dramatic differentiation defect in mouse embryonic stem cells (mESCs). Mechanistically, the m A deposited by METTL5 is involved in regulating the efficient translation of F-box and WD repeat domain-containing 7 (FBXW7), a key regulator of cell differentiation. Deficiency of METTL5 reduces FBXW7 levels and leads to the accumulation of its substrate c-MYC, thereby delaying the onset of mESC differentiation. Our study uncovers an important role of METTL5-mediated 18S m A in mESC differentiation through translation regulation and provides new insight into the functional significance of rRNA m A.
ISSN:1469-3178