Conserved tyrosine kinase promotes the import of silencing RNA into Caenorhabditis elegans cells
Conserved tyrosine kinase promotes the import of silencing RNA into Caenorhabditis elegans cells
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DOI：
10.1073/pnas.1201153109
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发表时间：
2012-09-04
影响因子：
11.1
通讯作者：
Hunter, Craig P.
中科院分区：
文献类型：
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作者：
Jose, Antony M.;Kim, Yunsoo A.;Hunter, Craig P.
秀丽隐杆线虫中的RNA沉默通过双链RNA（dsRNA）的运输在细胞之间传递。然而，这种传输的效率取决于细胞类型和环境。在这里，我们确定系统性RNAi缺陷-3（SID-3）作为有效导入dsRNA所需的保守酪氨酸激酶。在没有SID-3的情况下，细胞很好地进行RNA沉默，但输入dsRNA很差。当SID-3过表达时，细胞比野生型细胞更有效地输入dsRNA，并且这种dsRNA的有效输入需要完整的SID-3激酶结构域。SID-3的哺乳动物同源物，活化的cdc-42相关激酶（ACK），在响应环境变化的许多信号传导途径中起作用，并且已知直接与内吞囊泡相关，内吞囊泡涉及dsRNA转运。因此，我们的研究结果表明，SID-3/ACK酪氨酸激酶作为一个调节器的RNA输入到动物细胞。
RNA silencing in Caenorhabditis elegans is transmitted between cells by the transport of double-stranded RNA (dsRNA). The efficiency of such transmission, however, depends on both the cell type and the environment. Here, we identify systemic RNAi defective-3 (SID-3) as a conserved tyrosine kinase required for the efficient import of dsRNA. Without SID-3, cells perform RNA silencing well but import dsRNA poorly. Upon overexpression of SID-3, cells import dsRNA more efficiently than do wild-type cells and such efficient import of dsRNA requires an intact SID-3 kinase domain. The mammalian homolog of SID-3, activated cdc-42-associated kinase (ACK), acts in many signaling pathways that respond to environmental changes and is known to directly associate with endocytic vesicles, which have been implicated in dsRNA transport. Therefore, our results suggest that the SID-3/ACK tyrosine kinase acts as a regulator of RNA import into animal cells.