Michael W M, Choi M, Dreyfuss G
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104-6148, USA.
Cell. 1995 Nov 3;83(3):415-22. doi: 10.1016/0092-8674(95)90119-1.
Pre-mRNAs are associated with hnRNPs, and these proteins play important roles in the biogenesis of mRNAs. The hnRNP A1 is one of the most abundant hnRNPs, and although localized primarily in the nucleoplasm, shuttles continuously between the nucleus and the cytoplasm. A 38 amino acid domain within A1, termed M9, which bears no resemblance to classical nuclear localization signal (NLS) sequences, localizes A1 to the nucleus. Here we show that M9 is also a nuclear export signal; placing M9 on a protein that is otherwise restricted to the nucleus, the nucleoplasmin core domain (NPc), efficiently exports it to the cytoplasm in a temperature-dependent manner. In contrast, classical NLSs cannot promote the export of NPc. These findings demonstrate that there is a signal-dependent, temperature-sensitive nuclear export pathway and strengthen the suggestion that A1 and other shuttling hnRNPs function as carriers for RNA during export to the cytoplasm.
前体信使核糖核酸（pre-mRNAs）与核不均一核糖核蛋白（hnRNPs）相关联，并且这些蛋白质在信使核糖核酸（mRNAs）的生物合成中发挥重要作用。核不均一核糖核蛋白A1（hnRNP A1）是最丰富的核不均一核糖核蛋白之一，尽管它主要定位于核质中，但在细胞核和细胞质之间持续穿梭。A1内一个38个氨基酸的结构域，称为M9，它与经典的核定位信号（NLS）序列没有相似性，但能将A1定位于细胞核。在此我们表明M9也是一个核输出信号；将M9置于原本局限于细胞核的蛋白质——核纤层蛋白核心结构域（NPc）上，能以温度依赖的方式有效地将其输出到细胞质中。相比之下，经典的核定位信号不能促进NPc的输出。这些发现表明存在一种信号依赖的、温度敏感的核输出途径，并强化了这样一种观点，即A1和其他穿梭的核不均一核糖核蛋白在向细胞质输出过程中作为RNA的载体发挥作用。
