Autoantigen La Regulates MicroRNA Processing from Stem–Loop Precursors by Association with DGCR8,Biochemistry

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Autoantigen La Regulates MicroRNA Processing from Stem–Loop Precursors by Association with DGCR8
Biochemistry ( IF 2.9 ) Pub Date : 2017-11-08 00:00:00 , DOI: 10.1021/acs.biochem.7b00693
Quan Zheng ₁ , Hai-Jie Yang ₁ , Y. Adam Yuan _{1,

2}

Affiliation

In humans, primary microRNA (pri-miRNA) processing starts from precise cleavage of the stem loop, which is catalyzed by the Drosha–DGCR8 complex. However, the significant inconsistencies in the expression levels among primary, precursor, and mature miRNAs clearly indicate that many other factors may be involved in this regulation. Here, we utilize a newly developed RNA affinity technique to isolate such factors. In this study, a tRNA-scaffolded aptamer (tRSA)-based RNA affinity tag, by directly fusing primary let-7 miRNA to the 3′-end of tRSA, is employed to pull down the protein components specifically binding to pri-let-7. We show that La protein binds to pri-let-7 via its La motif and significantly promotes the processing efficiency of pri-let-7 in vitro and in cells. In addition, we demonstrate that La protein is associated with DGCR8, but not Drosha, in an RNA-dependent manner. Interestingly, the RNA binding capacity of La motif is important for miRNA processing. Hence, we propose that La protein is an important microprocessor component regulating miRNA processing efficiency by association with DGCR8 to regulate formation of the DGCR8–Drosha complex for miRNA processing.

中文翻译：

自身抗原La通过与DGCR8结合来调节茎环前体中的MicroRNA加工。

在人类中，主要的microRNA（pri-miRNA）处理始于茎环的精确切割，这是由Drosha-DGCR8复合物催化的。但是，初级，前体和成熟miRNA之间表达水平的显着不一致清楚地表明，许多其他因素可能也参与了该调控。在这里，我们利用新开发的RNA亲和力技术来分离这些因素。在这项研究中，通过直接将主要的let-7 miRNA融合到tRSA的3'末端，使用基于tRNA的适体（tRSA）的RNA亲和标签，将与pri-let- 7 我们表明La蛋白通过其La母题绑定到pri-let-7，并显着提高了pri-let-7在体外和细胞中的加工效率。此外，我们证明了La蛋白与DGCR8相关，但不是Drosha，而是依赖RNA的方式。有趣的是，La基序的RNA结合能力对于miRNA加工很重要。因此，我们认为La蛋白是通过与DGCR8结合来调节DGCR8-Drosha复合物形成miRNA的加工，从而调节miRNA加工效率的重要微处理器组件。

更新日期：2017-11-09

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