Cyclophilins (Cyps) catalyze the cis/trans isomerization of peptidyl- @entity10783 bonds, a rate-limiting step in protein folding. In some cases, cyclophilins have also been shown to form stable complexes with specific proteins in vivo and may thus also act as chaperone-like molecules. We have characterized the 20kD protein of the spliceosomal 25S [U4/U6.U5] tri- @entity12922 complex from HeLa cells and show that it is a novel @entity1 cyclophilin (denoted @entity42247 ). Purified [U4/U6.U5] tri-snRNPs, but not U1, U2, or U5 snRNPs, exhibit peptidyl- @entity10783 cis/trans isomerase activity in vitro, which is @entity205 -sensitive, suggesting that @entity42247 is an active isomerase. Consistent with its specific association with tri-snRNPs in vitro, immunofluorescence microscopy studies showed that @entity42247 is predominantly located in the nucleus, where it colocalizes in situ with typical @entity12922 -containing structures referred to as nuclear speckles. As a first step toward the identification of possible targets of @entity42247 , we have investigated the interaction of @entity42247 with other proteins of the tri- @entity12922 . Fractionation of RNA-free protein complexes dissociated from isolated tri-snRNPs by treatment with high salt revealed that @entity42247 is part of a biochemically stable heteromer containing additionally the U4/U6-specific 60kD and 90kD proteins. By coimmunoprecipitation experiments performed with in vitro-translated proteins, we could further demonstrate a direct interaction between @entity42247 and the 60kD protein, but failed to detect a protein complex containing the 90kD protein. The formation of a stable @entity42247 /60kD/90kD heteromer may thus require additional factors not present in our in vitro reconstitution system. We discuss possible roles of @entity42247 in the assembly of [U4/U6.U5] tri-snRNPs and/or in conformational changes occurring during the splicing process.

The 20kD protein of XXXX [U4/U6.U5] tri-snRNPs is a novel cyclophilin that forms a complex with the U4/U6-specific 60kD and 90kD proteins.

@entity1 :: ('9606', 'Species') :: ['human'] @entity42247 :: ('10465', 'Gene') :: ['SnuCyp-20'] @entity12922 :: ('57819', 'Gene') :: ['snRNP'] @entity205 :: ('MESH:D016572', 'Chemical') :: ['cyclosporin A'] @entity10783 :: ('CHEBI:26274', 'Chemical') :: ['prolyl']
@entity1 :: (9606,Species) :: ['human']
