来自美国马萨诸塞州医学院生物化学与分子药理学系的Phillip D. Zamore实验室发现Argonaute将RNA分出不同的功能和RNA结合组分,这篇文章刊登在最新一期《CELL》杂志上。

-2012年11月21日《细胞》


中文翻译


【题目】Argonaute将RNA分出不同的功能和RNA结合组分

【译文】miRNAs和siRNAs指导Argonaute蛋白沉默mRNA表达。Argonaute的结合改变了RNA引导的成分,形成了功能区域。我们发现Argonaute建立的区域(包括锚、种子、中心、3`端补充和尾部结构)具有不同的生化组成,这就解释了动物miRNAs和siRNAs结合靶标时存在的差异性。siRNA和其靶标的广泛互补性减慢了蝇Argonaute2 (Ago2)结合和分解靶标的速率。蝇Ago2在抗病毒中具有重要作用,它从互补性靶RNA上缓慢解离以至于所有成对靶标都被剪切。相反的是,主要调节miRNA指导的抑制的小鼠AGO2可以增加分解速率并且对所有成对的靶标速率相似。我们的数据缩减了以下生化合理模型的范围——Argonaute 结合的siRNAs和miRNAs发现、结合和调节它们的靶标。

英文原稿


[Title]Argonaute Divides Its RNA Guide into Domains with Distinct Functions and RNA-Binding Properties

[author]Liang Meng Wee, C. Fabián Flores-Jasso, William E. Salomon, Phillip D. Zamore

[Abstract]MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) guide Argonaute proteins to silence mRNA expression. Argonaute binding alters the properties of an RNA guide, creating functional domains. We show that the domains established by Argonaute—the anchor, seed, central, 3′ supplementary, and tail regions—have distinct biochemical properties that explain the differences between how animal miRNAs and siRNAs bind their targets. Extensive complementarity between an siRNA and its target slows the rate at which fly Argonaute2 (Ago2) binds to and dissociates from the target. Highlighting its role in antiviral defense, fly Ago2 dissociates so slowly from extensively complementary target RNAs that essentially every fully paired target is cleaved. Conversely, mouse AGO2, which mainly mediates miRNA-directed repression, dissociates rapidly and with similar rates for fully paired and seed-matched targets. Our data narrow the range of biochemically reasonable models for how Argonaute-bound siRNAs and miRNAs find, bind, and regulate their targets.

原文地址

http://www.cell.com/abstract/S0092-8674(12)01299-8

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