- 期刊
Nucleocytoplasmic Transport of Pre-mRNA Splicing Regulators
並列摘要
In eukaryotes, post-transeriptional events of gene expression involve RNA processing, export and turnover, and each of the steps can be regulated. Eukaryotic mRNAs are transcribed as precursors of which the introns are subsequently removed by the multi-component splicing machinery. A large family of serine/arginine-rich proteins (SR proteins) play important roles in both constitutive and regulated precursor mRNA splicing. In addition, they also participate in mRNA export and regulation of mRNA stability. Since a subset of SR proteins shuttle between the nucleus and the cytoplasm and their subcellular localization can be regulated by phosphorylation of the RS domain, we thus have been interested in the molecular mechanisms that govern nucleocytoplasmic transport of SR proteins. We previously identified a human importin-beta family protein, transportin-SR2 (TRN-SR2), that specifically interacts with phosphorylated SR proteins. In vitro import assays have revealed that TRN-SR2 is capable of targeting phosphorylated, but not unphosphorylated, SR proteins to the nucleus. Thus, RS domain phosphorylation is critical for TRN-SR2-mediated nuclear import. To understand more about TRN-SR2-mediated nuclcar transport, we searched for proteins that interact with the TRN-SR2 cargo-binding domain. We found several non-SR proteins as potential ligands to TRN-SR2, inclding the RNA-binding protein RBM4. TRN-SR2 interacted specifically with the C-terminal domain of RBM4 in yeast and in vitro. This domain served as a nuclear and speckle-targeting signal when fused to a heterologous protein. In vitro import assay next provided evidence that TRN-SR2 mediated nuclear import of the RBM4-fusion protein. Interestingly, we further found that RBM4 antagonized the effect of ASF/SF2 (an SR protein) on the alternative 5’splice site selection in vivo and in vitro. Therefore, TRN-SR2 may serve as a vehicle for pre-mRNA splicing regulators of opposing Activity to the nucleus, and perhaps thereby regulates alternative splicing of Pre-mRAN.
並列關鍵字
無資料延伸閱讀
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