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

RNA修飾による赤血球造血制御機構を解明 --RNAのメチル化がDNA修復に必要--. 京都大学プレスリリース. 2022-11-10.Mice show METTL in DNA blood repair: RNA methylation shows important role in erythropoiesis. 京都大学プレスリリース. 2022-11-25.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 expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis

Bombyx Vasa sequesters transposon mRNAs in nuage via phase separation requiring RNA binding and self-association

Bombyx Vasa assembles Vasa bodies, the site of transposon silencing by Siwi and Ago3-piRISC formation. Here, the authors show Vasa sequesters transposon mRNAs in Vasa bodies via phase separation requiring RNA binding and self-association of Vasa