Big Insights into Small RNAs.
Big Insights into Small RNAs.
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对小 RNA 的深入了解。
DOI：
10.1021/acs.biochem.0c00252
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Rissland,OliviaS
中科院分区：
文献类型：
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作者：
Rissland,OliviaS
自从被发现以来，microRNA (miRNA) 就一直让科学家们着迷。 miRNA 被加载到 Argonaute (Ago) 蛋白中形成 RNA 诱导的沉默复合物 (RISC)，在动物体内转录后抑制其靶标。它们主要通过破坏目标转录本的稳定性，并在某种程度上抑制翻译起始来实现这一点。每个动物 miRNA 都可以调节数百个靶基因，因此它们几乎影响每个生物过程。 1 但了解特定 miRNA 的生物学功能一直是一个持久的问题，因为科学家首先必须解决预测目标的关键问题，尽管进行了大量研究，但这一挑战仍然存在。然而，在令人兴奋的新工作中，David Bartel 及其同事在克服这一障碍方面迈出了重要的一步：他们发现 miRNA 与靶标相互作用的生化框架可用于预测靶标。 2miRNA靶向的语言是碱基配对。主要碱基配对发生在加载的 miRNA（核苷酸 2−7）的“种子”和相应的目标转录物之间。该核心区域周围的其他相互作用（例如与 miRNA 的核苷酸 8 配对或与核苷酸 1 相对的 A 配对）可能会导致更多的抑制。不同类型的位点在如何响应 miRNA 方面具有可预测的层次结构，这长期以来一直指导着目标预测算法。 1 更有效的靶标对 miRNA 具有更高的亲和力，这开启了生化方法预测 miRNA 靶标的可能性。事实上，生化测量已经量化了单个 miRNA 和靶序列之间的亲和力。 3, 4 然而，目前尚不可能将这些研究扩展到许多不同的位点和 miRNA，或将这些结果与体内介导的抑制联系起来。此外，许多类型的 miRNA 与靶标相互作用的重要性，特别是那些在种子相互作用中具有凸起和不匹配的相互作用（称为“非规范位点”），甚至更加不透明，因为不同的 miRNA 似乎表现不同。
Since their discovery, microRNAs (miRNAs) have fascinated scientists. Loaded into an Argonaute (Ago) protein to form an RNA-induced silencing complex (RISC), miRNAs posttranscriptionally repress their targets in animals. They do so predominantly by destabilizing target transcripts and, to some extent, by repressing translation initiation. Each animal miRNA can regulate hundreds of target genes, so they impact nearly every biological process. 1 But understanding the biological functions of a specific miRNA has been an enduring problem because a scientist first must wrestle with the critical issue of predicting targets, a challenge that persists despite a substantial amount of research. However, in exciting new work, David Bartel and colleagues have taken an important step forward in surmounting this obstacle: they have found that a biochemical framework for miRNA− target interactions can be harnessed for predicting targets. 2The language of miRNA targeting is base pairing. The main base pairing occurs between the “seed” of the loaded miRNA (nucleotides 2− 7) and the corresponding target transcript. Additional interactions around this core region (such as pairing with nucleotide 8 of the miRNA or an A opposite nucleotide 1) can lead to more repression. The different types of sites have a predictable hierarchy in how they respond to miRNAs, which has long guided target prediction algorithms. 1 More effective targets have higher affinities for the miRNA, which opens up the possibility of biochemical methods for predicting miRNA targets. Indeed, biochemical measurements have quantified the affinities between individual miRNAs and target sequences. 3, 4 However, it has not yet been possible to extend these studies to many different sites and miRNAs or to connect these results with the repression mediated in vivo. In addition, the importance of many types of miRNA− target interactions, especially those with bulges and mismatches in the seed interaction (called “noncanonical sites”), has been even more opaque because different miRNAs seem to behave differently.