mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations.
mRNA Location and Translation Rate Determine Protein Targeting to Dual Destinations.
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mRNA 位置和翻译率决定蛋白质靶向双重目的地。
DOI：
10.1101/2023.04.24.538105
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Mili,Stavroula
中科院分区：
文献类型：
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作者：
Gasparski,AlexanderN;Moissoglu,Konstadinos;Pallikkuth,Sandeep;Meydan,Sezen;Guydosh,NicholasR;Mili,Stavroula
许多蛋白质以两个或多个亚细胞为靶点，在那里它们发挥着不同的功能结果。这种差异靶向之间的平衡被认为是在翻译后决定的，依赖于蛋白质分类机制。在这里，我们证明了mRNA的位置和翻译速率也可以通过调节蛋白质与特定相互作用伙伴的结合来决定蛋白质靶向。NET1mRNA的外围定位和快速翻译通过促进Net1蛋白与膜相关支架蛋白桶的结合，提高了Net1蛋白的胞浆保留率。相反，核周mRNA的定位和/或较慢的翻译速率通过促进与重要蛋白的结合而有利于核靶向。这种依赖于mRNA位置的机制受到生理刺激的调节，并深刻地影响了Net1在细胞运动中的功能。这些结果表明，蛋白质合成的位置和翻译延伸率作为一种“伙伴选择”机制协同作用，有力地影响了蛋白质的分布和功能。
Numerous proteins are targeted to two or multiple subcellular destinations where they exert distinct functional consequences. The balance between such differential targeting is thought to be determined post-translationally, relying on protein sorting mechanisms. Here, we show that mRNA location and translation rate can also determine protein targeting by modulating protein binding to specific interacting partners. Peripheral localization of theNET1mRNA and fast translation lead to higher cytosolic retention of the NET1 protein by promoting its binding to the membrane-associated scaffold protein CASK. By contrast, perinuclear mRNA location and/or slower translation rate favor nuclear targeting by promoting binding to importins. This mRNA location-dependent mechanism is modulated by physiological stimuli and profoundly impacts NET1 function in cell motility. These results reveal that the location of protein synthesis and the rate of translation elongation act in coordination as a "partner-selection" mechanism that robustly influences protein distribution and function.