A NEW CYCLOPHILIN AND THE HUMAN HOMOLOGS OF YEAST PRP3 AND PRP4 FORM A COMPLEX-ASSOCIATED WITH U4 U6 SNRNPS/

We have purified three new human U4/U6-snRNP proteins from HeLa cells. The three proteins formed a tightly bound complex and behaved as a si ngle species throughout the purification. All three proteins have been identified by peptide sequencing, and full-length cDNA sequences have been obtained for all of them. Two of the proteins are homologues of the Saccharomyces cerevisiae splicing factors Prp3 and Prp4, and the t hird protein is a cyclophilin. Both the human and S. cerevisiae Prp4 p roteins have seven repeats of the WD motif and likely fold into struct ures very similar to those of the beta subunits of G proteins. The hum an Prp3 protein is highly basic and is closely related to S. cerevisia e Prp3 only in its carboxyl-terminal half. The human homologues of Prp 3 and Prp4 are part of a stable complex in the absence of RNA. The thi rd protein in the complex is a new cyclophilin. Cyclophilins have been proposed to act as chaperones in a variety of cellular processes, and we discuss some possible roles of this U4/U6 snRNP-associated cycloph ilin.