Open AccessFMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation
Author(s) -
Haibo Yang,
Yumin Wang,
Yufei Xiang,
Tribhuwan Yadav,
Jie Ouyang,
Laiyee Phoon,
Xueping Zhu,
Yi Shi,
Lee Zou,
Li Lan
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116251119
Subject(s) - dna demethylation , transcription (linguistics) , rna , messenger rna , biology , homologous recombination , demethylation , dna repair , dna , microbiology and biotechnology , dna methylation , chemistry , genetics , gene , gene expression , linguistics , philosophy
Significance This study shows that Fragile X mental retardation protein (FMRP) promotes messenger RNA (mRNA)-dependent recombination via facilitating ten-eleven translocation protein 1 (TET1)-mediated mRNA methyl-5-cytosine (m5C) demethylation. Loss of FMRP leads to damage induced mRNA m5C and R-loop accumulation at sites of active transcription, defective recombination repair, and increased radiosensitivity of tumor cells. FMRP-dependent RNA m5C demethylation and R-loop resolving during DNA repair are important for repair completion and the maintenance of genome stability. The removal of m5C by the FMRP–TET1 axis is coupled with R-loop dissolution, which ensures proper completion of DNA repair and survival of cells after DNA damage. These findings significantly advance our understanding of the regulation of RNA modifications in R-loop dynamics during DNA repair.