The N⁶-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity.

ABSTRACT: During erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N⁶-methyladenosine (m⁶A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m⁶A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their e

SUBMITTER: Yoshinaga M 

PROVIDER: S-EPMC9616860 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature