Nonclassical nuclear localization signals mediate nuclear import of CIRBP
Nonclassical nuclear localization signals mediate nuclear import of CIRBP
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DOI：
10.1073/pnas.1918944117
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发表时间：
2020-04-14
影响因子：
11.1
通讯作者：
Madl, Tobias
中科院分区：
文献类型：
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作者：
Bourgeois, Benjamin;Hutten, Saskia;Madl, Tobias
进口蛋白与货物蛋白的核定位信号（NLSs）的特异性相互作用不仅介导了核的进口，而且阻止了它们在细胞质中的异常相分离和胁迫颗粒的募集。输入蛋白转运蛋白-1 （TNPO1）在这两个过程的（病理）生理中起关键作用。在这里，我们报道TNPO1和转运蛋白-3 （TNPO3）都识别冷诱导rna结合蛋白（CIRBP）中的两个非经典NLSs。我们的生物物理研究表明，TNPO1识别一个富含精氨酸-甘氨酸（-甘氨酸）（RG/RGG）的区域，而TNPO3识别一个富含精氨酸-丝氨酸-酪氨酸（RSY）残基的区域。这些相互作用调节细胞中CIRBP的核定位、相分离和应力颗粒募集。RG/RGG和RSY区域存在于许多其他rna结合蛋白中，这表明TNPO1和TNPO3与这些非经典NLSs的相互作用可能调节无膜细胞器的形成和许多蛋白质的亚细胞定位。
The specific interaction of importins with nuclear localization signals (NLSs) of cargo proteins not only mediates nuclear import but also, prevents their aberrant phase separation and stress granule recruitment in the cytoplasm. The importin Transportin-1 (TNPO1) plays a key role in the (patho-)physiology of both processes. Here, we report that both TNPO1 and Transportin-3 (TNPO3) recognize two nonclassical NLSs within the cold-inducible RNA-binding protein (CIRBP). Our biophysical investigations show that TNPO1 recognizes an arginine-glycine(-glycine) (RG/RGG)-rich region, whereas TNPO3 recognizes a region rich in arginine-serine-tyrosine (RSY) residues. These interactions regulate nuclear localization, phase separation, and stress granule recruitment of CIRBP in cells. The presence of both RG/RGG and RSY regions in numerous other RNA-binding proteins suggests that the interaction of TNPO1 and TNPO3 with these non-classical NLSs may regulate the formation of membraneless organelles and subcellular localization of numerous proteins.