Abstract:
:RNA modifications represent a novel layer of regulation of gene expression. Functional experiments revealed that N6 -methyladenosine (m6 A) on messenger RNA (mRNA) plays critical roles in cell fate determination and development. m6 A mark also resides in the decoding center of 18S ribosomal RNA (rRNA); however, the biological function of m6 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 m6 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 m6 A in mESC differentiation through translation regulation and provides new insight into the functional significance of rRNA m6 A.
journal_name
EMBO Repjournal_title
EMBO reportsauthors
Xing M,Liu Q,Mao C,Zeng H,Zhang X,Zhao S,Chen L,Liu M,Shen B,Guo X,Ma H,Chen H,Zhang Jdoi
10.15252/embr.201949863subject
Has Abstractpub_date
2020-10-05 00:00:00pages
e49863issue
10eissn
1469-221Xissn
1469-3178journal_volume
21pub_type
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