Roles of Prolyl Isomerases in RNA-Mediated Gene Expression.
Roles of Prolyl Isomerases in RNA-Mediated Gene Expression.
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DOI：
10.3390/biom5020974
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发表时间：
2015-05-18
期刊：
影响因子：
5.5
通讯作者：
Thapar R
中科院分区：
文献类型：
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作者：
Thapar R
肽基-脯氨酰顺反异构酶 (PPIase) 包括亲免蛋白（亲环蛋白和 FKBP）和小病毒蛋白（Pin1、Par14、Par17），参与细胞信号传导、转录、前 mRNA 加工和 mRNA 降解。人类基因组编码 19 个亲环蛋白、18 个 FKBP 和 3 个小病毒蛋白。亲免素是器官移植中使用的免疫抑制药物环孢菌素 A、FK506 和雷帕霉素的受体。 Pin1 还被用于治疗阿尔茨海默病、哮喘和多种癌症。虽然这些 PPIase 被称为分子伴侣，但它们也以非伴侣方式发挥作用，利用其活性位点之外的表面促进蛋白质-蛋白质相互作用。免疫抑制药物通过促进体内蛋白质-蛋白质相互作用，通过功能获得机制发挥作用。几种亲免蛋白已被鉴定为剪接体的成分，并且对于选择性剪接至关重要。 Pin1 通过催化 RNA Pol II C 末端结构域的构象变化在转录和 RNA 加工中发挥作用。 Pin1 还结合多种 RNA 结合蛋白，例如 AUF1、KSRP、HuR 和 SLBP，这些蛋白通过重塑 mRNP 复合物来调节 mRNA 衰减。核糖核蛋白相关 PPI 酶的功能很大程度上未知。这篇综述重点介绍了在 RNA 介导的基因表达中发挥作用的 PPIase，深入了解它们在体内 mRNP 重塑中的结构、功能和作用机制。
The peptidyl-prolyl cis-trans isomerases (PPIases) that include immunophilins (cyclophilins and FKBPs) and parvulins (Pin1, Par14, Par17) participate in cell signaling, transcription, pre-mRNA processing and mRNA decay. The human genome encodes 19 cyclophilins, 18 FKBPs and three parvulins. Immunophilins are receptors for the immunosuppressive drugs cyclosporin A, FK506, and rapamycin that are used in organ transplantation. Pin1 has also been targeted in the treatment of Alzheimer’s disease, asthma, and a number of cancers. While these PPIases are characterized as molecular chaperones, they also act in a nonchaperone manner to promote protein-protein interactions using surfaces outside their active sites. The immunosuppressive drugs act by a gain-of-function mechanism by promoting protein-protein interactions in vivo. Several immunophilins have been identified as components of the spliceosome and are essential for alternative splicing. Pin1 plays roles in transcription and RNA processing by catalyzing conformational changes in the RNA Pol II C-terminal domain. Pin1 also binds several RNA binding proteins such as AUF1, KSRP, HuR, and SLBP that regulate mRNA decay by remodeling mRNP complexes. The functions of ribonucleoprotein associated PPIases are largely unknown. This review highlights PPIases that play roles in RNA-mediated gene expression, providing insight into their structures, functions and mechanisms of action in mRNP remodeling in vivo.