Biochemistry

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Science  08 Feb 2002:
Vol. 295, Issue 5557, pp. 931-933
DOI: 10.1126/science.295.5557.931e

Cyclophilin was first identified as the cellular target of the immunosuppressive drug cyclosporin; it also possesses a prolyl isomerase activity and binds proline-containing peptides. However, the in vivo function of this family of proteins remains unclear: Are they needed to flip the prolyl peptide bonds, or do they serve as chaperones that stabilize particular protein conformations? Attempts to untangle these putative roles have been stymied by the inability to disable one activity without disrupting the other.

Horowitz et al. examined the catalytic and structural participation of the cyclophilin USA-CyP in the splicing of pre- messenger RNA (pre-mRNA). USA-CyP binds to the human splicing factors hPrp4 and hPrp18. hPrP4 is required for assembly of the spliceosome complex that mediates the first half-reaction (separating the 5' end of the intron from the pre-mRNA), and hPrP18 is required during the second half-reaction (removing the intron and joining exons). These structural interactions differ from those of cyclophilins and HIV capsid proteins, in that binding occurs at a site distinct from the catalytic center. Thus cyclophilin can be added to the list of choreographers who direct the sequential rearrangements of RNA and protein that occur during pre-mRNA splicing. — GJC

EMBO J.21, 470 (2002).

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