19 0

Mettl1/Wdr4-Mediated m(7)G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation

Title
Mettl1/Wdr4-Mediated m(7)G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation
Author
최준호
Keywords
YEAST TRANSFER-RNA; GENE; METHYLATION; REVEALS; COMPLEX; WDR4; 7-METHYLGUANOSINE; PHENOTYPE; FORM; CODE
Issue Date
2018-07
Publisher
CELL PRESS
Citation
MOLECULAR CELL, v. 71, no. 2, page. 244-255.e5
Abstract
tRNAs are subject to numerous modifications, including methylation. Mutations in the human N-7-methylguanosine (m(7)G) methyltransferase complex METTL1/WDR4 cause primordial dwarfism and brain malformation, yet the molecular and cellular function in mammals is not well understood. We developed m(7)G methylated tRNA immunoprecipitation sequencing (MeRIP-seq) and tRNA reduction and cleavage sequencing (TRAC-seq) to reveal the m(7)G tRNA methylome in mouse embryonic stem cells (mESCs).A subset of 22 tRNAs is modified at a ''RAGGU'' motif within the variable loop. We observe increased ribosome occupancy at the corresponding codons in Mettl1 knockout mESCs, implying widespread effects on tRNA function, ribosome pausing, and mRNA translation. Translation of cell cycle genes and those associated with brain abnormalities is particularly affected. Mettl1 or Wdr4 knockout mESCs display defective self-renewal and neural differentiation. Our study uncovers the complexity of the mammalian m(7)G tRNA methylome and highlights its essential role in ESCs with links to human disease.
URI
https://www.cell.com/molecular-cell/fulltext/S1097-2765(18)30443-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS109727651830443X%3Fshowall%3Dtruehttp://repository.hanyang.ac.kr/handle/20.500.11754/119331
ISSN
1097-2765; 1097-4164
DOI
10.1016/j.molcel.2018.06.001
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE