HNS, a nuclear-cytoplasmic shuttling sequence in HuR

HNS, a nuclear-cytoplasmic shuttling sequence in HuR
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DOI:
10.1073/pnas.95.26.15293
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发表时间:
1998-12-22
影响因子:
11.1
通讯作者:
Steitz, JA
Steitz, JA
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fan, XHC;Steitz, JA

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蛋白质通过特定信号运入和运出细胞核。两个最好的研究核运输过程介导的经典核定位信号或核输出信号。也有穿梭序列指导RNA结合蛋白的双向运输。两个例子是异质核核糖核蛋白Al中的M9序列和异质核核糖核蛋白K中的异质核核糖核蛋白K穿梭结构域(KNS)序列,这两者似乎都对mRNA向细胞质的输出有重要贡献。HuR是一种RNA结合蛋白,可稳定在其3'非翻译区含有富含AU元件的不稳定mRNA,并已显示在细胞核和细胞质之间穿梭(18,19)。我们在HuR中发现了一个穿梭序列,它也具有转录依赖的核定位信号活性。我们建议,HuR首先可以结合富含AU元素的mRNA在细胞核中,然后护送它们通过核孔,在出口到细胞质隔室期间和之后提供保护。
Proteins are transported into and out of the cell nucleus via specific signals. The two best-studied nuclear transport processes are mediated either by classical nuclear localization signals or nuclear export signals. There also are shuttling sequences that direct the bidirectional transport of RNA-binding proteins. Two examples are the M9 sequence in heterogeneous nuclear ribonucleoprotein Al and the heterogeneous nuclear ribonucleoprotein K shuttling domain (KNS) sequence in heterogeneous nuclear ribonucleoprotein K, both of which appear to contribute importantly to the export of mRNA to the cytoplasm. HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm (18, 19). We have identified in HuR a shuttling sequence that also possess transcription-dependent nuclear localization signal activity. We propose that HuR first may bind AU-rich element-containing mRNAs in the nucleus and then escort them through the nuclear pore, providing protection during and after export to the cytoplasmic compartment.