rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-2-1
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pubmed:abstractText |
We report that the cyclophilin USA-CyP is part of distinct complexes with two spliceosomal proteins and is involved in both steps of pre-mRNA splicing. The splicing factors hPrp18 and hPrp4 have a short region of homology that defines a high affinity binding site for USA-CyP in each protein. USA-CyP forms separate, stable complexes with hPrp18 and hPrp4 in which the active site of the cyclophilin is exposed. The cyclophilin inhibitor cyclosporin A slows pre-mRNA splicing in vitro, and we show that its inhibition of the second step of splicing is caused by blocking the action of USA-CyP within its complex with hPrp18. Cyclosporin A also slows splicing in vivo, and we show that this slowing results specifically from inhibition of USA-CyP. Our results lead to a model in which USA-CyP is carried into the spliceosome in complexes with hPrp4 and hPrp18, and USA-CyP acts during splicing within these complexes. These results provide an example of the function of a cyclophilin in a complex process and provide insight into the mechanisms of action of cyclophilins.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11823439-10025408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11823439-10199565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11823439-10329631,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
21
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
470-80
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:11823439-Amino Acid Sequence,
pubmed-meshheading:11823439-Cyclophilins,
pubmed-meshheading:11823439-HeLa Cells,
pubmed-meshheading:11823439-Humans,
pubmed-meshheading:11823439-Molecular Sequence Data,
pubmed-meshheading:11823439-Nuclear Proteins,
pubmed-meshheading:11823439-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11823439-RNA Precursors,
pubmed-meshheading:11823439-RNA Splicing,
pubmed-meshheading:11823439-RNA-Binding Proteins,
pubmed-meshheading:11823439-Ribonucleoprotein, U4-U6 Small Nuclear
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pubmed:year |
2002
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pubmed:articleTitle |
A cyclophilin functions in pre-mRNA splicing.
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pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. dhorowitz@usuhs.mil
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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