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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Nuclear cyclophilins affect spliceosome assembly and function in vitro
Biochemical journal, v 469(2), pp 223-233
13 May 2015
PMID: 25967372
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse
cis/trans
isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for
in vitro
pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing
in vitro
. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function
in vitro
. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.
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Details
- Title
- Nuclear cyclophilins affect spliceosome assembly and function in vitro
- Creators
- B.M. Adams - University of California, Santa CruzMiranda N. Coates - University of California, Santa CruzS. RaElle Jackson - Drexel UniversityMelissa S. Jurica - University of California, Santa CruzTara L. Davis - Drexel UniversityAlexandra Rochelle Vaughn
- Publication Details
- Biochemical journal, v 469(2), pp 223-233
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000361051800007
- Scopus ID
- 2-s2.0-84937153236
- Other Identifier
- 991019357632604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology