N⁶-Methyladenosine on mRNA facilitates a phase-separated nuclear body that suppresses myeloid leukemic differentiation.

ABSTRACT: N⁶-Methyladenosine (m⁶A) on mRNAs mediates different biological processes and its dysregulation contributes to tumorigenesis. How m⁶A dictates its diverse molecular and cellular effects in leukemias remains unknown. We found that YTHDC1 is the essential m⁶A reader in myeloid leukemia from a genome-wide CRISPR screen and that m⁶A is required for YTHDC1 to undergo liquid-liquid phase separation and form nuclear YTHDC1-m⁶A condensates (nYACs). The number of nYACs increases in acute myeloid leukemia (AML) cells compared with normal hematopoietic stem and progenitor cells. AML cells require the nYACs to maintain cell survival and the undifferentiated state that is critical for leukemia maintenance. Furthermore, nYACs enable YTHDC

SUBMITTER: Cheng Y 

PROVIDER: S-EPMC8282764 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature