European Molecular Biology Laboratory, Mouse Biology Unit, Monterotondo Scalo, 00015, Italy.
J Exp Med. 2010 Jul 5;207(7):1351-8. doi: 10.1084/jem.20100458. Epub 2010 May 31.
The process of erythropoiesis must be efficient and robust to supply the organism with red bloods cells both under condition of homeostasis and stress. The microRNA (miRNA) pathway was recently shown to regulate erythroid development. Here, we show that expression of the locus encoding miR-144 and miR-451 is strictly dependent on Argonaute 2 and is required for erythroid homeostasis. Mice deficient for the miR-144/451 cluster display a cell autonomous impairment of late erythroblast maturation, resulting in erythroid hyperplasia, splenomegaly, and a mild anemia. Analysis of gene expression profiles from wild-type and miR-144/451-deficient erythroblasts revealed that the miR-144/451 cluster acts as a "tuner" of gene expression, influencing the expression of many genes. MiR-451 imparts a greater impact on target gene expression than miR-144. Accordingly, mice deficient in miR-451 alone exhibited a phenotype indistinguishable from miR-144/451-deficient mice. Thus, the miR-144/451 cluster tunes gene expression to impart a robustness to erythropoiesis that is critical under conditions of stress.
红细胞生成过程必须高效且稳健，以便在维持体内平衡和应激状态下为机体提供红细胞。最近的研究表明，microRNA（miRNA）通路可以调节红细胞的发育。在这里，我们发现编码 miR-144 和 miR-451 的基因座的表达严格依赖于 Argonaute 2，并且是红细胞维持体内平衡所必需的。miR-144/451 簇缺失的小鼠表现出晚期红系母细胞成熟的自主缺陷，导致红细胞增生、脾肿大和轻度贫血。对野生型和 miR-144/451 缺失的红系细胞的基因表达谱进行分析表明，miR-144/451 簇作为一种“调谐器”来影响基因表达，影响许多基因的表达。miR-451 对靶基因表达的影响大于 miR-144。因此，单独缺乏 miR-451 的小鼠表现出与 miR-144/451 缺失的小鼠无法区分的表型。因此，miR-144/451 簇通过调节基因表达赋予红细胞生成稳健性，这在应激条件下至关重要。
