RNA recognition by Roquin in posttranscriptional gene regulation
RNA recognition by Roquin in posttranscriptional gene regulation
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Roquin 在转录后基因调控中的 RNA 识别
DOI：
10.1002/wrna.1333
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sattler M
中科院分区：
文献类型：
--
作者：
Schlundt A;Niessing D;Heissmeyer V;Sattler M
基因表达的转录后调节在先天性和适应性免疫应答的启动中起着核心作用。Roquin蛋白就是一个例子，由于其预防自身免疫的能力，在过去十年中引起了极大的兴趣。Roquin通过限制T细胞表面共刺激受体的诱导表达来控制T细胞活化和T辅助细胞分化。它通过其ROQ结构域（一种新的RNA结合折叠）识别靶转录物3′ UTR中的顺式调节RNA发夹元件，并通过募集介导去腺苷化和去帽的因子来触发它们的降解。最近的结构研究揭示了ROQ结构域识别RNA发夹结构的分子细节。令人惊讶的是，发现Roquin主要依赖于RNA的形状特异性识别。这一观察结果意味着更广泛的RNA基序可以与蛋白质相互作用，但它也使系统搜索Roquin的新mRNA靶点变得复杂。因此，需要大规模的方法，如交联和免疫沉淀或通过指数富集实验结合下一代测序的配体系统进化，以鉴定其靶RNA的完整谱。结合它们结合模式的结构分析，这将使我们能够解开Roquin和其他反式作用因子对3′ UTR调控的复杂性。在这里，我们回顾了我们目前对Roquin-RNA相互作用及其对Roquin功能的作用的理解。WIRES RNA 2016，7：455-469。土井：10.1002/wrna.1333这篇文章分类下：RNA与蛋白质和其他分子的相互作用>蛋白质-RNA抑制RNA与蛋白质和其他分子的相互作用> RNA-蛋白质复合物RNA周转和监视> RNA稳定性的调节
Posttranscriptional regulation of gene expression plays a central role in the initiation of innate and adaptive immune responses. This is exemplified by the protein Roquin, which has attracted great interest during the past decade owing to its ability to prevent autoimmunity. Roquin controls T‐cell activation and T helper cell differentiation by limiting the induced expression of costimulatory receptors on the surface of T cells. It does so by recognizingcisregulatory RNA‐hairpin elements in the 3′ UTR of target transcripts via its ROQ domain—a novel RNA‐binding fold—and triggering their degradation through recruitment of factors that mediate deadenylation and decapping. Recent structural studies have revealed molecular details of the recognition of RNA hairpin structures by the ROQ domain. Surprisingly, it was found that Roquin mainly relies on shape‐specific recognition of the RNA. This observation implies that a much broader range of RNA motifs could interact with the protein, but it also complicates systematic searches for novel mRNA targets of Roquin. Thus, large‐scale approaches, such as crosslinking and immunoprecipitation or systematic evolution of ligands by exponential enrichment experiments coupled with next‐generation sequencing, will be required to identify the complete spectrum of its target RNAs. Together with structural analyses of their binding modes, this will enable us to unravel the intricate complexity of 3′ UTR regulation by Roquin and othertrans‐acting factors. Here, we review our current understanding of Roquin–RNA interactions and their role for Roquin function.WIREs RNA2016, 7:455–469. doi: 10.1002/wrna.1333This article is categorized under:RNA Interactions with Proteins and Other Molecules > Protein–RNA RecognitionRNA Interactions with Proteins and Other Molecules > RNA–Protein ComplexesRNA Turnover and Surveillance > Regulation of RNA Stability
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影响因子：
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