SUMOylation of TARBP2 regulates miRNA/siRNA efficiency.
SUMOylation of TARBP2 regulates miRNA/siRNA efficiency.
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TARBP2 的 SUMO 化调节 miRNA/siRNA 效率
DOI：
10.1038/ncomms9899
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发表时间：
2015-11-19
影响因子：
16.6
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Chen C;Zhu C;Huang J;Zhao X;Deng R;Zhang H;Dou J;Chen Q;Xu M;Yuan H;Wang Y;Yu J
小RNA诱导的基因沉默对于基因表达的转录后调节是必不可少的;然而，仍然不清楚miRNA/siRNA效率是如何调节的。在这里，我们发现TARBP 2在K52处被SUMO化，这可以通过其磷酸化来增强。这种修饰可以通过抑制其K48连接的泛素化来稳定TARBP 2。我们发现TARBP 2 SUMO化不影响成熟miRNA的整体产生，但它调节miRNA/siRNA的效率。SUMO化的TARBP 2募集Ago 2以构成RNA诱导的沉默复合物（RISC）加载复合物（RLC），并同时促进更多的前体miRNA加载到RLC中。因此，Ago 2被稳定化，并且被TARBP 2/Dicer结合的miRNA/siRNA被有效地转移到Ago 2。因此，这些过程导致RNA干扰（RNAi）的有效RISC的形成。总的来说，我们的数据表明，TARBP 2的SUMO化是调节miRNA/siRNA效率所必需的，这是miRNA/siRNA调节的一般机制。
Small RNA-induced gene silencing is essential for post-transcriptional regulation of gene expression; however, it remains unclear how miRNA/siRNA efficiency is regulated. Here we show that TARBP2 is SUMOylated at K52, which can be enhanced by its phosphorylation. This modification can stabilize TARBP2 via repressing its K48-linked ubiquitination. We find that TARBP2 SUMOylation does not influence the overall production of mature miRNAs, but it regulates miRNA/siRNA efficiency. SUMOylated TARBP2 recruits Ago2 to constitute the RNA-induced silencing complex (RISC)-loading complex (RLC), and simultaneously promotes more pre-miRNAs to load into the RLC. Consequently, Ago2 is stabilized and miRNAs/siRNAs bound by TARBP2/Dicer is effectively transferred to Ago2. Thus, these processes lead to the formation of the effective RISC for RNA interference (RNAi). Collectively, our data suggest that SUMOylation of TARBP2 is required for regulating miRNA/siRNA efficiency, which is a general mechanism of miRNA/siRNA regulation.