MOV10 and FMRP regulate AGO2 association with microRNA recognition elements.
MOV10 and FMRP regulate AGO2 association with microRNA recognition elements.
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DOI：
10.1016/j.celrep.2014.10.054
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发表时间：
2014-12-11
期刊：
影响因子：
8.8
通讯作者：
Ceman S
中科院分区：
文献类型：
--
作者：
Kenny PJ;Zhou H;Kim M;Skariah G;Khetani RS;Drnevich J;Arcila ML;Kosik KS;Ceman S
脆性X智力低下蛋白FMRP通过不完全定义的机制调节其结合mRNA的翻译。FMRP与microRNA通路有关，我们在这里展示了它与RNA解旋酶MOV 10相关，MOV 10也与microRNA通路相关。FMRP与MOV 10直接相关，并以RNA依赖的方式促进MOV 10与脑和细胞中的RNA相关，表明合作相互作用。我们使用RNA-IP和iCLIP鉴定了由MOV 10识别的RNA。对MOV 10在RNA上的命运的检查揭示了MOV 10在调节翻译中的双重功能：它促进了一些RNA的微RNA介导的翻译，但也通过阻止AGO 2功能来增加其他RNA的表达。后一个子集也被FMRP结合在靠近MOV 10结合位点处，表明FMRP阻止MOV 10介导的microRNA抑制。我们已经确定了一个新的机制，FMRP介导的翻译调控，通过其与MOV 10。
The fragile X mental retardation protein FMRP regulates translation of its bound mRNAs through incompletely defined mechanisms. FMRP has been linked to the microRNA pathway and we show here that it associates with the RNA helicase MOV10, also associated with the microRNA pathway. FMRP associates with MOV10 directly and in an RNA-dependent manner and facilitates MOV10-association with RNAs in brain and cells suggesting a cooperative interaction. We identified the RNAs recognized by MOV10 using RNA-IP and iCLIP. Examination of the fate of MOV10 on RNAs revealed a dual function for MOV10 in regulating translation: it facilitates microRNA-mediated translation of some RNAs but also increases expression of other RNAs by preventing AGO2 function. The latter subset was also bound by FMRP in close proximity to the MOV10 binding site, suggesting that FMRP prevents MOV10-mediated microRNA suppression. We have identified a new mechanism for FMRP-mediated translational regulation through its association with MOV10.
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