Matrin CYP, an SR-rich Cyclophilin That Associates with the Nuclear Matrix and Splicing Factors*
Abstract
We report the identification and cloning of a nuclear matrix protein termed matrin cyclophilin or matrin CYP. The derived sequence of matrin cyp encodes a protein of 752 amino acids with a predicted mass of 88 kDa. A 172-residue stretch at the amino terminus shows high identity with the ubiquitous family of cyclophilins. Clustered throughout the carboxyl half of the protein are a series of serine-arginine (SR) repeats that are a characteristic feature of many RNA splicing factors. Antibodies raised against matrin CYP recognize a 106-kDa antigen that is detected in isolated nuclei and quantitatively subfractionates in the nuclear matrix. Laser scanning confocal microscopy localizes most of the anti-matrin CYP-specific antigen within the nucleus in a pattern of large bright speckles that co-localize with splicing factors and diffuse nucleoplasmic staining. A strikingly similar pattern of staining is observed in cells extracted for in situ nuclear matrices. A fusion protein containing the cyclophilin domain of matrin CYP exhibits cyclosporin A (CsA)-sensitive, peptidylprolyl cis-trans-isomerase activity that is characteristic of native cyclophilins. Although total rat liver nuclei contains predominantly CsA-resistant PPIase activity, the corresponding activity in the nuclear matrix is largely CsA-sensitive.
Footnotes
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↵* This work was supported by National Institutes of Health Grant GM 23922 (to R. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) AF043642.
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↵‡ To whom correspondence should be addressed: Dept. of Biological Sciences, State University of New York, Buffalo, NY 14260. Tel.: 716-645-2363; Fax: 716-645-2975; E-mail:Berezney{at}acsu.buffalo.edu.
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↵1 The abbreviations used are: RNP, ribonucleoprotein; snRNP, small nuclear ribonucleoprotein; CYP, cyclophilin; CsA, cyclosporin A; CTD, carboxyl-terminal domain of RNA polymerase II large subunit; DTT, dithiothreitol; GST, glutathioneS-transferase; NK-TR, natural killer tumor recognition molecule; NLS, nuclear localization signal; PBS, phosphate-buffered saline; PPIase, peptidylprolyl cis-trans-isomerase; pol II, polymerase II; bp, base pair(s); AAPF, Ala-Ala-Pro-Phe; DAPI, 4,6-diamidino-2-phenylindole.
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- Received December 15, 1997.
- Revision received January 23, 1998.
- The American Society for Biochemistry and Molecular Biology, Inc.
