Promoter-bound METTL3 maintains myeloid leukaemia by m⁶A-dependent translation control.

ABSTRACT: N⁶-methyladenosine (m⁶A) is an abundant internal RNA modification in both coding and non-coding RNAs that is catalysed by the METTL3-METTL14 methyltransferase complex. However, the specific role of these enzymes in cancer is still largely unknown. Here we define a pathway that is specific for METTL3 and is implicated in the maintenance of a leukaemic state. We identify METTL3 as an essential gene for growth of acute myeloid leukaemia cells in two distinct genetic screens. Downregulation of METTL3 results in cell cycle arrest, differentiation of leukaemic cells and failure to establish leukaemia in immunodeficient mice. We show that METTL3, independently of METTL14, associates with chromatin and localizes to the transcriptional start sites of active genes. The vast maj

SUBMITTER: Barbieri I 

PROVIDER: S-EPMC6217924 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature