The N6‐methyladenosine ( m ⁶ A) methyltransferase Wilms tumour 1‐associating protein promotes erythr

Summary

Anaemia is a common global health problem affecting more than 500 million people worldwide. While N6‐methyladenosine (m ⁶ A) methylation is recognized as the most abundant internal (messenger ribonucleic acid (mRNA) modification that governs haematopoiesis, its specific function in erythropoiesis remains poorly understood. Here, we demonstrate that Wilms tumour 1‐associating protein (WTAP), a core component of the m ⁶ A methyltransferase complex, is highly expressed in erythroid progenitors and is expressed at low levels during differentiation. Depletion of WTAP compromises erythropoiesis both in vivo and in vitro, characterized by a profound reduction in erythroid progenitors and increased erythroblast apoptosis. Mechanistically, our findings demonstrate that WTAP‐mediated m ⁶ A modification is indispensable for maintaining normal erythropoiesis, orchestrating a broader regulatory network in which the signal transducer and activator of transcription 5 (STAT5) pathway acts as a critical, albeit not exclusive, downstream effector.