M³C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.

ABSTRACT: The epitranscriptome includes a diversity of RNA modifications that influence gene expression. N3-methylcytidine (m³C) mainly occurs in the anticodon loop (position C32) of certain tRNAs yet its role is poorly understood. Here, using HAC-Seq, we report comprehensive METTL2A/2B-, METTL6-, and METTL2A/2B/6-dependent m³C profiles in human cells. METTL2A/2B modifies tRNA-arginine and tRNA-threonine members, whereas METTL6 modifies the tRNA-serine family. However, decreased m³C32 on tRNA-Ser-GCT isodecoders is only observed with combined METTL2A/2B/6 deletion. Ribo-Seq reveals altered translation of genes related to cell cycle and DNA repair pathways in METTL2A/2B/6-deficient cells, and these mRNAs are enriched in AGU codons that require tRNA-Ser-GCT for transla

SUBMITTER: Cui J 

PROVIDER: S-EPMC11233606 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature