The N⁶-methyladenosine (m⁶A)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells.

ABSTRACT: N⁶-methyladenosine (m⁶A) is an abundant nucleotide modification in mRNA that is required for the differentiation of mouse embryonic stem cells. However, it remains unknown whether the m⁶A modification controls the differentiation of normal and/or malignant myeloid hematopoietic cells. Here we show that shRNA-mediated depletion of the m⁶A-forming enzyme METTL3 in human hematopoietic stem/progenitor cells (HSPCs) promotes cell differentiation, coupled with reduced cell proliferation. Conversely, overexpression of wild-type METTL3, but not of a catalytically inactive form of METTL3, inhibits cell differentiation and increases cell growth. METTL3 mRNA and protein are expressed more abundantly in acute myeloid leukemia (AML) cells than in healthy HSPC

SUBMITTER: Vu LP 

PROVIDER: S-EPMC5677536 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature