MicroRNA1 influences cardiac differentiation in Drosophila and regulates notch signaling
MicroRNA1 influences cardiac differentiation in Drosophila and regulates notch signaling
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DOI：
10.1073/pnas.0509535102
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发表时间：
2005-12-27
影响因子：
11.1
通讯作者：
Srivastava, D
中科院分区：
文献类型：
--
作者：
Kwon, C;Han, Z;Srivastava, D
微小RNA（miRNAs）是基因组编码的小分子RNA，它们与信使RNA杂交，导致靶转录本的降解或翻译抑制。miRNAs在调节细胞谱系决定或从多能祖细胞或干细胞分化方面的潜力尚不清楚。在此，我们表明微小RNA1（miR - 1）是一个古老的肌肉特异性基因，其在果蝇中的序列和表达具有保守性。果蝇的miR - 1（dmiR - 1）通过心脏祖细胞中一个血清反应因子样结合位点受到调控。功能缺失和功能获得研究表明dmiR - 1在调节心脏发生以及维持肌肉基因表达中起作用。我们提供了体内证据，表明dmiR - 1靶向编码Notch配体Delta的转录本，这为心脏和肌肉祖细胞的扩增以及某些dmiR - 1突变体中祖细胞分化失败提供了一种潜在机制。这些发现表明，dmiR - 1可能“微调”心脏和体肌祖细胞分化所涉及的关键步骤，并靶向祖细胞特化和不对称细胞分裂所需的途径。
MicroRNAs (miRNAs) are genomically encoded small RNAs that hybridize with messenger RNAs, resulting in degradation or translational inhibition of targeted transcripts. The potential for miRNAs to regulate cell-lineage determination or differentiation from pluripotent progenitor or stem cells is unknown. Here, we show that rnicroRNA1 (miR-1) is an ancient muscle-specif ic gene conserved in sequence and expression in Drosophila. Drosophila miR-1 (dmiR-1) is regulated through a serum response factor-like binding site in cardiac progenitor cells. Loss-and gain-of-function studies demonstrated a role for dmiR-1 in modulating cardiogenesis and in maintenance of muscle-gene expression. We provide in vivo evidence that dmiR-1 targets transcripts encoding the Notch ligand Delta, providing a potential mechanism for the expansion of cardiac and muscle progenitor cells and failure of progenitor cell differentiation in some dmiR-1 mutants. These findings demonstrate that dmiR-1 may "fine-tune" critical steps involved in differentiation of cardiac and somatic muscle progenitors and targets a pathway required for progenitor cell specification and asymmetric cell division.