Splicing factor hSlu7 contains a unique functional domain required to retain the protein within the nucleus.
Splicing factor hSlu7 contains a unique functional domain required to retain the protein within the nucleus.
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DOI：
10.1091/mbc.e04-02-0152
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发表时间：
2004-08
影响因子：
3.3
通讯作者：
N. Shomron;Mika Reznik;G. Ast
中科院分区：
文献类型：
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作者：
N. Shomron;Mika Reznik;G. Ast
前体mRNA剪接去除内含子并连接外显子以形成成熟mRNA。这一过程是在一个剪接体复合物中进行的，该复合物含有>150种蛋白质和5种小的核核糖核蛋白。剪接蛋白hSlu7是正确选择3'剪接位点所必需的。在这里，我们通过生物信息学和突变分析确定了hSlu7蛋白在其亚细胞定位中具有不同作用的三个功能域：核定位信号，锌关节基序和富含赖氨酸的区域。锌关节基序嵌入在核定位信号中的独特功能结构中，该结构不是hSlu7进入核所需的，而是将hSlu7维持在核内，防止其通过染色体区域维持1途径穿梭回到细胞质。因此，hSlu7的锌节基序通过核质敏感的穿梭平衡决定蛋白质的细胞定位。总之，这表明锌依赖性核质穿梭可能是细胞核内hSlu7蛋白水平调节的可能分子基础。
Precursor-mRNA splicing removes the introns and ligates the exons to form a mature mRNA. This process is carried out in a spliceosomal complex containing >150 proteins and five small nuclear ribonucleoproteins. Splicing protein hSlu7 is required for correct selection of the 3' splice site. Here, we identify by bioinformatics and mutational analyses three functional domains of the hSlu7 protein that have distinct roles in its subcellular localization: a nuclear localization signal, a zinc-knuckle motif, and a lysine-rich region. The zinc-knuckle motif is embedded within the nuclear localization signal in a unique functional structure that is not required for hSlu7's entrance into the nucleus but rather to maintain hSlu7 inside it, preventing its shuttle back to the cytoplasm via the chromosomal region maintenance 1 pathway. Thus, the zinc-knuckle motif of hSlu7 determines the cellular localization of the protein through a nucleocytoplasmic-sensitive shuttling balance. Altogether, this indicates that zinc-dependent nucleocytoplasmic shuttling might be the possible molecular basis by which hSlu7 protein levels are regulated within the nucleus.