Silencing by small RNAs is linked to endosomal trafficking.
Silencing by small RNAs is linked to endosomal trafficking.
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DOI：
10.1038/ncb1930
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发表时间：
2009-09
影响因子：
21.3
通讯作者：
Carthew, Richard W.
中科院分区：
文献类型：
--
作者：
Lee, Young Sik;Pressman, Sigal;Andress, Arlise P.;Kim, Kevin;White, Jamie L.;Cassidy, Justin J.;Li, Xin;Lubell, Kim;Lim, Do Hwan;Cho, Ik Sang;Nakahara, Kenji;Preall, Jonathan B.;Bellare, Priya;Sontheimer, Erik J.;Carthew, Richard W.
小RNA直接诱导RNA沉默复合体(RISCs)调节mRNAs的稳定性和翻译。与靶向mRNAs相关的RISCs通常聚集在离散的细胞质内，称为GW小体。然而，RISC蛋白可以与高尔基体和内质网等膜间隔结合。在这里，我们发现GW小体与晚期内小体或多囊泡小体(MVB)相关。通过丢失拴系因子HPS4来阻止MVB转化为溶酶体，从而增强果蝇和人类中siRNA和miRNA介导的沉默。它还会触发GW小体的过度积累。通过ESCRT耗尽阻断MVB的形成会导致细胞中miRNA沉默和GW小体丢失。这些结果表明，有源RISC在物理上和功能上都与MVB相耦合。我们进一步表明，MVB促进了RISC加载小RNA的能力。我们建议MVB促进RISC的回收，以便更有效地与小RNA效应器和可能的靶向RNA接触。它可能提供一种手段来增强细胞质中RNA沉默的动力学。
Small RNAs direct RNA induced silencing complexes (RISCs) to regulate the stability and translation of mRNAs. RISCs associated with target mRNAs often accumulate in discrete cytoplasmic foci known as GW-bodies. However, RISC proteins can associate with membrane compartments such as the Golgi and ER. Here, we show that GW-bodies are associated with late endosomes or multivesicular bodies (MVBs). Blocking turnover of MVBs into lysosomes by loss of the tethering factor HPS4, enhances siRNA- and miRNA-mediated silencing in Drosophila and humans. It also triggers over-accumulation of GW-bodies. Blocking MVB formation by ESCRT depletion results in impaired miRNA silencing and loss of GW-bodies in cells. These results indicate that active RISC is physically and functionally coupled to MVBs. We further show that MVBs promote the competence of RISC to load small RNAs. We suggest that recycling of RISC is promoted by MVBs in order to more effectively engage with small RNA effectors and possibly target RNAs. It may provide a means to enhance the dynamics of RNA silencing in the cytoplasm.
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影响因子：
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通讯作者：
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