Regulation of miRNA strand selection: follow the leader?
Regulation of miRNA strand selection: follow the leader?
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DOI：
10.1042/bst20140142
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发表时间：
2014-08-01
影响因子：
3.9
通讯作者：
Bushell, Martin
中科院分区：
文献类型：
--
作者：
Meijer, Hedda A.;Smith, Ewan M.;Bushell, Martin
miRNA链选择是决定miRNA双链中哪一条链成为被纳入RISC （rna诱导沉默复合体）的活性链（称为引导链，引导链或miR），哪一条链被降解（乘客链或miR*）的过程。双相的热力学特性似乎在这一决定中起着重要作用；在其5'端结合最弱的链更有可能成为引导链。人类miRNA引导链的其他关键特征是在5‘端有u型偏倚和过量的嘌呤，而客运链在5’端有c型偏倚和过量的嘧啶。已知有几种蛋白质在链选择中起作用[Ago (Argonaute)， DICER， TRBP（反式激活反应rna结合蛋白），PACT （dsrna依赖性蛋白激酶的蛋白激活因子）和Xrn-1/2]；然而，这些蛋白质的作用机制在很大程度上是未知的。对于一些mirna， miR/miR*的比例取决于细胞类型、发育阶段和不同的疾病状态，这表明链选择是一个严格控制的过程。本综述讨论了我们目前对链选择的因素和过程的了解以及仍然存在的许多问题。
miRNA strand selection is the process that determines which of the two strands in a miRNA duplex becomes the active strand that is incorporated into the RISC (RNA-induced silencing complex) (named the guide strand, leading strand or miR) and which one gets degraded (the passenger strand or miR*). Thermodynamic features of the duplex appear to play an important role in this decision; the strand with the weakest binding at its 5'-end is more likely to become the guide strand. Other key characteristics of human miRNA guide strands are a U-bias at the 5'-end and an excess of purines, whereas the passenger strands have a C-bias at the 5'-end and an excess of pyrimidines. Several proteins are known to play a role in strand selection [Ago (Argonaute), DICER, TRBP (trans-activation response RNA-binding protein), PACT (protein activator of dsRNA-dependent protein kinase) and Xrn-1/2]; however, the mechanisms by which these proteins act are largely unknown. For several miRNAs the miR/miR* ratio varies dependent on cell type, developmental stage and in different disease states, suggesting that strand selection is a tightly controlled process. The present review discusses our current knowledge regarding the factors and processes involved in strand selection and the many questions that still remain.