New insights into functional roles of the polypyrimidine tract-binding protein.

New insights into functional roles of the polypyrimidine tract-binding protein.
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DOI:
10.3390/ijms141122906
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发表时间:
2013-11-20
影响因子:
5.6
通讯作者:
Lievens PM
Lievens PM
中科院分区:
生物学2区
文献类型:
--
作者:
Romanelli MG;Diani E;Lievens PM

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多嘧啶结合蛋白(PTB)是一种被广泛研究的RNA结合蛋白,参与多种基因表达的转录后调控事件。PTB最初被描述为一种前mRNA剪接调节因子,现在被广泛认为是一种穿梭于细胞核和细胞质之间的多功能蛋白质。因此,PTB可以与选定的RNA靶标、结构元件和蛋白质相互作用。越来越多的证据表明,PTB及其类似的PTBP2作为选择性剪接外显子的抑制因子发挥了重要作用,其转录受组织调控。除了选择性剪接,PTB几乎参与了mRNA代谢的所有步骤,包括多聚腺苷化、mRNA稳定性和启动蛋白质翻译。此外,众所周知,PTB在内部核糖体进入位点(IRES)的募集激活了微小核糖体病毒和细胞蛋白的翻译。对PTB结构性质的详细研究有助于我们理解RNA识别基序(RRM)结构域与RNA结合的机制。在本综述中,我们将描述结核分枝杆菌的结构特性、其类似物和辅助因子、在转录后调节中的作用以及在细胞分化和发病机制中的作用。明确PTB的多功能作用将有助于理解基因表达中的关键调控事件。
Polypyrimidine Tract Binding Protein (PTB) is an intensely studied RNA binding protein involved in several post-transcriptional regulatory events of gene expression. Initially described as a pre-mRNA splicing regulator, PTB is now widely accepted as a multifunctional protein shuttling between nucleus and cytoplasm. Accordingly, PTB can interact with selected RNA targets, structural elements and proteins. There is increasing evidence that PTB and its paralog PTBP2 play a major role as repressors of alternatively spliced exons, whose transcription is tissue-regulated. In addition to alternative splicing, PTB is involved in almost all steps of mRNA metabolism, including polyadenylation, mRNA stability and initiation of protein translation. Furthermore, it is well established that PTB recruitment in internal ribosome entry site (IRES) activates the translation of picornaviral and cellular proteins. Detailed studies of the structural properties of PTB have contributed to our understanding of the mechanism of RNA binding by RNA Recognition Motif (RRM) domains. In the present review, we will describe the structural properties of PTB, its paralogs and co-factors, the role in post-transcriptional regulation and actions in cell differentiation and pathogenesis. Defining the multifunctional roles of PTB will contribute to the understanding of key regulatory events in gene expression.
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