美国德克萨斯大学西南医学中心Joshua T. Mendell研究组取得最新进展。他们指出泛素连接酶介导靶标指导的MicroRNA（miRNA）衰变，与拖尾和修剪无关。2020年11月12日出版的《科学》杂志上。

他们鉴定了一个cullin-ring泛素连接酶（CRL），其中包含介导靶标指导的microRNA降解（TDMD）的底物衔接子ZSWIM8。ZSWIM8 CRL与Argonaute（AGO）蛋白相互作用，以不依赖拖尾和修整的方式促进TDMD，并调节多种细胞类型中的miRNA表达。这些发现提示了一种模型，其中ZSWIM8泛素连接酶通过指导与高度互补靶标结合且含miRNA复合体的蛋白酶体降解来介导TDMD。

研究人员表示，MicroRNA（miRNA）与AGO蛋白协同作用，以抑制靶标mRNA。AGO装载后，miRNA通常显示缓慢的更新。当miRNA遇到高度互补的靶标时，会发生一个重要的例外，这可能会触发称为TDMD过程。在TDMD过程中，miRNA经历拖尾和修剪，这表明这是衰变机制中的重要一步。

附：英文原文

Title: A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming

Author: Jaeil Han, Collette A. LaVigne, Benjamin T. Jones, He Zhang, Frank Gillett, Joshua T. Mendell

Issue&Volume: 2020/11/12

Abstract: MicroRNAs (miRNAs) act in concert with Argonaute (AGO) proteins to repress target mRNAs. After AGO loading, miRNAs generally exhibit slow turnover. An important exception occurs when miRNAs encounter highly complementary targets, which can trigger a process termed target-directed microRNA degradation (TDMD). During TDMD, miRNAs undergo tailing and trimming, suggesting that this is an important step in the decay mechanism. Here, we identified a cullin-RING ubiquitin ligase (CRL), containing the substrate adapter ZSWIM8, that mediated TDMD. The ZSWIM8 CRL interacted with AGO proteins, promoted TDMD in a tailing and trimming-independent manner, and regulated miRNA expression in multiple cell types. These findings suggest a model in which the ZSWIM8 ubiquitin ligase mediates TDMD by directing proteasomal decay of miRNA-containing complexes engaged with highly complementary targets.

DOI: 10.1126/science.abc9546

Source: https://science.sciencemag.org/content/early/2020/11/11/science.abc9546