通过ADAR脱氨酶进行RNA编辑对微小RNA加工和表达的调控。
Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.
作者信息
Yang Weidong, Chendrimada Thimmaiah P, Wang Qingde, Higuchi Miyoko, Seeburg Peter H, Shiekhattar Ramin, Nishikura Kazuko
机构信息
The Wistar Institute, 3601 Spruce Street, Philadelphia, Pennsylvania 19104, USA.
出版信息
Nat Struct Mol Biol. 2006 Jan;13(1):13-21. doi: 10.1038/nsmb1041. Epub 2005 Dec 20.
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.
作用于RNA的腺苷脱氨酶（ADARs）参与双链RNA（dsRNA）中腺苷残基向肌苷的编辑过程。尽管这种编辑会重新编码并改变多个哺乳动物基因的功能，但其最常见的靶点是非编码重复序列，这表明该编辑系统除了参与蛋白质序列的重新编码外，还涉及目前未知的其他功能。在此我们表明，特定微小RNA（miRNA）前体的特定腺苷残基会被ADAR1和ADAR2编辑。在造血组织中表达的miRNA - 142的前体pri - miR - 142的编辑导致其被Drosha加工的过程受到抑制。编辑后的pri - miR - 142被Tudor - SN降解，Tudor - SN是RNA诱导沉默复合体（RISC）的一个组成部分，也是一种对含肌苷的dsRNA具有特异性的核糖核酸酶。因此，在ADAR1基因敲除或ADAR2基因敲除的小鼠中，成熟miRNA - 142的表达水平大幅增加。我们的结果证明了RNA编辑在控制miRNA生物合成中的新功能。
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