Biogenesis of mammalian microRNAs by a non-canonical processing pathway.
Biogenesis of mammalian microRNAs by a non-canonical processing pathway.
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DOI：
10.1093/nar/gks026
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发表时间：
2012-05
影响因子：
14.9
通讯作者：
Hastings ML
中科院分区：
文献类型：
--
作者：
Havens MA;Reich AA;Duelli DM;Hastings ML
典型的microRNA生物发生需要微处理器组件Drosha和DGCR 8来产生miRNA，Dicer来形成成熟的miRNA。微处理器不需要处理一些miRNA，包括mirtron，其中剪接体切除的内含子是直接Dicer底物。在这项研究中，我们研究了假定的人类mirtron的加工过程，并证明，虽然有些是剪接依赖的，正如预期的那样，预测的mirtron，miR-1225和miR-1228，在没有剪接的情况下产生。值得注意的是，敲除细胞系和敲低实验证明，这些剪接独立的mirtron样miRNA（称为“simtron”）的生物发生不需要典型的miRNA生物发生组分DGCR 8、Dicer、Exportin-5或Argonaute 2。然而，simtron生物合成减少了Drosha的显性阴性形式的表达。Simtron被Drosha结合并以Drosha依赖性方式在体外加工。simtron和mirtron都在靶转录物的沉默中起作用，并且在RISC复合物中发现，如通过它们与Argonaute蛋白的相互作用所证明的。这些发现揭示了一个非经典的miRNA生物合成途径，可以产生功能性调控RNA。
Canonical microRNA biogenesis requires the Microprocessor components, Drosha and DGCR8, to generate precursor-miRNA, and Dicer to form mature miRNA. The Microprocessor is not required for processing of some miRNAs, including mirtrons, in which spliceosome-excised introns are direct Dicer substrates. In this study, we examine the processing of putative human mirtrons and demonstrate that although some are splicing-dependent, as expected, the predicted mirtrons, miR-1225 and miR-1228, are produced in the absence of splicing. Remarkably, knockout cell lines and knockdown experiments demonstrated that biogenesis of these splicing-independent mirtron-like miRNAs, termed ‘simtrons’, does not require the canonical miRNA biogenesis components, DGCR8, Dicer, Exportin-5 or Argonaute 2. However, simtron biogenesis was reduced by expression of a dominant negative form of Drosha. Simtrons are bound by Drosha and processed in vitro in a Drosha-dependent manner. Both simtrons and mirtrons function in silencing of target transcripts and are found in the RISC complex as demonstrated by their interaction with Argonaute proteins. These findings reveal a non-canonical miRNA biogenesis pathway that can produce functional regulatory RNAs.
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影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
影响因子：
16
作者：
Bogerd HP;Karnowski HW;Cai X;Shin J;Pohlers M;Cullen BR
通讯作者：
Cullen BR
影响因子：
10.5
作者：
Chong, Mark M. W.;Zhang, Guoan;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
10.5
作者：
Babiarz, Joshua E.;Ruby, J. Graham;Blelloch, Robert
通讯作者：
Blelloch, Robert
DOI：
10.1126/science.1190809
发表时间：
2010-06-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cifuentes D;Xue H;Taylor DW;Patnode H;Mishima Y;Cheloufi S;Ma E;Mane S;Hannon GJ;Lawson ND;Wolfe SA;Giraldez AJ
通讯作者：
Giraldez AJ