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A cyclophilin functions in pre‐mRNA splicing
Author(s) -
Horowitz David S.,
Lee Edward J.,
Mabon Stephen A.,
Misteli Tom
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.3.470
Subject(s) - library science , gerontology , medicine , computer science
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.