Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, USA.
J Cell Mol Med. 2021 Mar;25(5):2377-2389. doi: 10.1111/jcmm.16067. Epub 2021 Jan 26.
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.
几十年来，红细胞去核的精确分子机制一直是一个基本的生物学问题。在这项研究中，我们发现 miR-144/451 对红细胞分化和去核起关键调节作用。我们进一步鉴定出 CAP1，一种 G-肌动蛋白结合蛋白，是 miR-144/451 在这些过程中的直接靶标。在终末红细胞生成过程中，CAP1 的表达随着 miR-144/451 水平的逐渐增加而下降。强制 CAP1 上调抑制了红细胞收缩肌动环的形成，并阻止了它们的终末分化和去核。我们的研究结果揭示了 CAP1 在 miR-144/451 介导的红细胞生成中的负调控作用，从而阐明了 microRNA 如何通过调节肌动蛋白动力学来精细调节终末红细胞发育。
