The Tetrahymena argonaute-binding protein Giw1p directs a mature argonaute-siRNA complex to the nucleus.
The Tetrahymena argonaute-binding protein Giw1p directs a mature argonaute-siRNA complex to the nucleus.
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DOI：
10.1016/j.cell.2010.02.010
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发表时间：
2010-03-05
期刊：
影响因子：
64.5
通讯作者：
Mochizuki K
中科院分区：
文献类型：
--
作者：
Noto T;Kurth HM;Kataoka K;Aronica L;DeSouza LV;Siu KW;Pearlman RE;Gorovsky MA;Mochizuki K
新出现的证据表明，RNAi相关的过程在细胞质和细胞核中都起作用。然而，RNAi机制被运送到细胞核中的过程仍然知之甚少。四膜虫Argonaute蛋白Twi 1 p定位于细胞核，对于小RNA指导的程序化DNA消除至关重要。在这项研究中，我们确定Giw 1 p，它结合到Twi 1 p，并需要其核定位。此外，Twi 1 p的内切核糖核酸酶（Slicer）活性在去除Twi 1 p相关siRNA的两条链中的一条中起着至关重要的作用，导致功能成熟的Twi 1 p-siRNA复合物。切片活性也被证明是必需的Twi 1 p的核定位和其协会与Giw 1 p。这些结果表明，Giw 1 p感知Twi 1 p相关siRNA的状态，并选择性地将成熟的Twi 1 p-siRNA复合物转运到细胞核中。
Emerging evidence suggests that RNAi-related processes act both in the cytoplasm and in the nucleus. However, the process by which the RNAi machinery is transported into the nucleus remains poorly understood. The Tetrahymena Argonaute protein Twi1p localizes to the nucleus and is crucial for small RNA-directed programmed DNA elimination. In this study, we identify Giw1p, which binds to Twi1p and is required for its nuclear localization. Further, the endoribonuclease (Slicer)-activity of Twi1p plays a vital role in the removal of one of the two strands of Twi1p-associated siRNAs, leading to a functionally mature Twi1p-siRNA complex. Slicer activity is also shown to be required for nuclear localization of Twi1p and for its association with Giw1p. These results suggest that Giw1p senses the state of Twi1p-associated siRNAs and selectively transports the mature Twi1p-siRNA complex into the nucleus.
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