Department of Biochemistry, Memorial University of Newfoundland, 45 Arctic Avenue, St. John's NL A1C 5S7, Canada.
Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea.
Nucleic Acids Res. 2023 Sep 22;51(17):9385-9396. doi: 10.1093/nar/gkad619.
MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and instead relies on AGO2 for its maturation. miR-451 is highly expressed in erythrocytes and regulates the differentiation of erythroblasts into mature red blood cells. However, the mechanistic details underlying miR-451 biogenesis in erythrocytes remains obscure. Here, we report that the RNA binding protein CSDE1 which is required for the development of erythroblasts into erythrocytes, controls the expression of miR-451 in erythroleukemia cells. CSDE1 binds miR-451 and regulates AGO2 processing of pre-miR-451 through its N-terminal domains. CSDE1 further interacts with PARN and promotes the trimming of intermediate miR-451 to the mature length. Together, our results demonstrate that CSDE1 promotes biogenesis of miR-451 in erythroid progenitors.
微 RNA 是由 RNase III 酶 Drosha 和 Dicer 依次加工的。miR-451 是脊椎动物中高度保守的 miRNA，它绕过 Dicer 加工，而是依赖 AGO2 来成熟。miR-451 在红细胞中高度表达，调节成红细胞向成熟红细胞的分化。然而，miR-451 在红细胞中的生物发生的机制细节仍然不清楚。在这里，我们报告说，RNA 结合蛋白 CSDE1 是红细胞发育所必需的，它控制着红细胞白血病细胞中 miR-451 的表达。CSDE1 结合 miR-451，并通过其 N 端结构域调节 pre-miR-451 的 AGO2 加工。CSDE1 还与 PARN 相互作用，并促进中间 miR-451 的修剪至成熟长度。总之，我们的结果表明，CSDE1 促进了红细胞祖细胞中 miR-451 的生物发生。
