Regulation of N6-methyladenosine modification in erythropoiesis and thalassemia

In eukaryotic RNA, N-6-methyladenosine (m(6)A) is a prevalent form of methylation modification. The m(6)A modification process is reversible and dynamic, written by m(6)A methyltransferase complex, erased by m(6)A demethylase, and recognized by m(6)A binding proteins. Through mediating RNA stability, decay, alternative splicing, and translation processes, m(6)A modification regulates gene expression at the post-transcriptional level. Erythropoiesis is the process of hematopoietic stem cells undergoing proliferation, a series of differentiation and maturation to form red blood cells (RBCs). Thalassemia is a common monogenic disease characterized by excessive production of ineffective RBCs in the peripheral circulation, resulting in hemolytic anemia. Increasing evidence suggests that m(6)A modification plays a crucial role in erythropoiesis. In this review, we comprehensively summarize the function of m(6)A modification in erythropoiesis and further generalize the mechanism of m(6)A modification regulating ineffective erythropoiesis and fetal hemoglobin expression. The purpose is to improve the understanding of the pathogenesis of erythroid dysplasia and offer new perspectives for the diagnosis and treatment of thalassemia.