Your browser doesn't support javascript.
loading
m3C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response.
Cui, Jia; Sendinc, Erdem; Liu, Qi; Kim, Sujin; Fang, Jaden Y; Gregory, Richard I.
Afiliación
  • Cui J; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.
  • Sendinc E; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
  • Liu Q; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.
  • Kim S; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
  • Fang JY; Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, 02115, USA.
  • Gregory RI; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA.
Nat Commun ; 15(1): 5775, 2024 Jul 10.
Article en En | MEDLINE | ID: mdl-38982125
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 translation. These results, supported by reporter assays, help explain the observed altered cell cycle, slowed proliferation, and increased cisplatin sensitivity phenotypes of METTL2A/2B/6-deficient cells. Thus, we define METTL2A/2B/6-dependent methylomes and uncover a particular requirement of m3C32 tRNA modification for serine codon-biased mRNA translation of cell cycle, and DNA repair genes.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina / Biosíntesis de Proteínas / Daño del ADN / Codón / ARN Mensajero / ARN de Transferencia / Ciclo Celular Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Serina / Biosíntesis de Proteínas / Daño del ADN / Codón / ARN Mensajero / ARN de Transferencia / Ciclo Celular Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido