Mettl1/Wdr4-Mediated m⁷G tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation.

ABSTRACT: tRNAs are subject to numerous modifications, including methylation. Mutations in the human N⁷-methylguanosine (m⁷G) methyltransferase complex METTL1/WDR4 cause primordial dwarfism and brain malformation, yet the molecular and cellular function in mammals is not well understood. We developed m⁷G methylated tRNA immunoprecipitation sequencing (MeRIP-seq) and tRNA reduction and cleavage sequencing (TRAC-seq) to reveal the m⁷G 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 ce

SUBMITTER: Lin S 

PROVIDER: S-EPMC6086580 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature