Biomolecules 2015, 5(2), 974-999; doi:10.3390/biom5020974
Roles of Prolyl Isomerases in RNA-Mediated Gene Expression
BioSciences at Rice-Biochemistry and Cell Biology, Rice University, Houston, TX 77251-1892, USA
Academic Editor: André P. Gerber
Received: 31 March 2015 / Revised: 1 May 2015 / Accepted: 7 May 2015 / Published: 18 May 2015
(This article belongs to the Special Issue RNA-Binding Proteins—Structure, Function, Networks and Disease)
Abstract
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. View Full-TextKeywords:
prolyl isomerase; cyclophilin; FKBP; parvulin; Pin1; histone mRNA; SLBP; KSRP; AUF1; HuR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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MDPI and ACS Style
Thapar, R. Roles of Prolyl Isomerases in RNA-Mediated Gene Expression. Biomolecules 2015, 5, 974-999.
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