CAP1, a target of miR-144/451, negatively regulates erythroid differentiation and enucleation.

ABSTRACT

The exact molecular mechanism underlying erythroblast enucleation has been a fundamental biological question for decades. In this study, we found that miR-144/451 critically regulated erythroid differentiation and enucleation. We further identified CAP1, a G-actin-binding protein, as a direct target of miR-144/451 in these processes. During terminal erythropoiesis, CAP1 expression declines along with gradually increased miR-144/451 levels. Enforced CAP1 up-regulation inhibits the formation of contractile actin rings in erythroblasts and prevents their terminal differentiation and enucleation. Our findings reveal a negative regulatory role of CAP1 in miR-144/451-mediated erythropoiesis and thus shed light on how microRNAs fine-tune terminal erythroid development through regulating actin dynamics.