英国剑桥MCR分子生物学实验室Ramanujan S. Hegde研究组取得一项新进展。他们发现TTC5蛋白通过mRNA降解介导微管蛋白的自动调节。相关论文于2019年11月14日在线发表于国际学术期刊《科学》。

研究人员确定了TTC5（tetratricopeptide protein 5）为微管蛋白特异性核糖体相关因子，通过响应过量的可溶性微管蛋白，从而触发微管蛋白mRNA的共翻译降解。结构分析表明，TTC5结合在核糖体出口通道附近，并与新生微管蛋白的N末端结合。无法与核糖体或新生微管蛋白相互作用的TTC5突变体不能对微管蛋白进行自动调节，并在有丝分裂过程中显示出染色体分离缺陷。这些发现揭示了，一类mRNA如何能够被靶向从而被特定的因子通过识别这些mRNA编码出的新生多肽来进行降解。

据介绍，微管蛋白在细胞分裂、细胞内运输和细胞形状中起关键作用。微管蛋白浓度通过未知机制通过对mRNA降解的反馈控制来自动调节。

附：英文原文

Title: TTC5 mediates autoregulation of tubulin via mRNA degradation

Author: Zhewang Lin, Ivana Gasic, Viswanathan Chandrasekaran, Niklas Peters, Sichen Shao, Timothy J. Mitchison, Ramanujan S. Hegde

Issue&Volume: 2019/11/14

Abstract: AbstractTubulins play crucial roles in cell division, intracellular traffic, and cell shape. Tubulin concentration is autoregulated by feedback control of mRNA degradation via an unknown mechanism. Here, we identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers co-translational degradation of tubulin mRNAs in response to excess soluble tubulin. Structural analysis revealed that TTC5 binds near the ribosome exit tunnel and engages the N terminus of nascent tubulins. TTC5 mutants incapable of ribosome or nascent tubulin interaction abolished tubulin autoregulation and showed chromosome segregation defects during mitosis. Our findings show how a subset of mRNAs can be targeted for coordinated degradation by a specificity factor that recognizes the nascent polypeptides they encode.

DOI: 10.1126/science.aaz4352

Source: https://science.sciencemag.org/content/early/2019/11/13/science.aaz4352