Modulation of microRNA processing and expression through RNA editing by ADAR deaminases
Modulation of microRNA processing and expression through RNA editing by ADAR deaminases
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DOI：
10.1038/nsmb1041
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发表时间：
2006-01-01
影响因子：
16.8
通讯作者：
Nishikura, K
中科院分区：
文献类型：
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作者：
Yang, WD;Chendrimada, TP;Nishikura, K
作用于RNA的腺苷脱氨酶（ADAR）参与将双链RNA（dsRNA）中的腺苷残基编辑为肌苷。虽然这种编辑重新编码并改变了几种哺乳动物基因的功能，但其最常见的目标是非编码重复序列，这表明这种编辑系统参与了目前未知的功能，而不是重新编码蛋白质序列。在这里，我们发现某些microRNA（miRNA）前体的特定腺苷残基由ADAR 1和ADAR 2编辑。编辑在造血组织中表达的pri-miR-142（miRNA-142的前体）导致Drosha抑制其加工。编辑的pri-miR- 142被Tudor-SN降解，Tudor-SN是RISC的组分，也是对含肌苷的dsRNA具有特异性的核糖核酸酶。因此，成熟的miRNA-142表达水平在ADAR 1缺失或ADAR 2缺失小鼠中显著增加。我们的研究结果证明了RNA编辑在控制miRNA生物合成中的新功能。
Adenosine deaminases acting on RNA (ADARs) are involved in editing of adenosine residues to inosine in double-stranded RNA ( dsRNA). Although this editing recodes and alters functions of several mammalian genes, its most common targets are noncoding repeat sequences, indicating the involvement of this editing system in currently unknown functions other than recoding of protein sequences. Here we show that specific adenosine residues of certain microRNA ( miRNA) precursors are edited by ADAR1 and ADAR2. Editing of pri - miR-142, the precursor of miRNA-142, expressed in hematopoietic tissues, resulted in suppression of its processing by Drosha. The edited pri - miR- 142 was degraded by Tudor-SN, a component of RISC and also a ribonuclease specific to inosine-containing dsRNAs. Consequently, mature miRNA-142 expression levels increased substantially in ADAR1 null or ADAR2 null mice. Our results demonstrate a new function of RNA editing in the control of miRNA biogenesis.