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Nucleic Acids Research, 1994, Vol. 22, No. 21 4510-4519
© 1994

MOLECULAR BIOLOGY

SWAP pre-mRNA splicing regulators are a novel, ancient protein family sharing a highly conserved sequence motif with the prp21 family of constitutive splicing proteins

Deborah A. spikes, Joseph Kramer, Paul M. Bingham* and Kevin Van Doren1

Department of Biochemistry and Cell Biology 450 Life Sciences Building University of New York Stony Brook, Ny 11794 1Department of Biology, Syracuse University Syracuse, NY 13244, USA

*To whom correspondence should be addressed

Received May 12, 1994. Revised August 22, 1994. Accepted August 22, 1994.

Regulators responsible for the pervasive, nonsexspecific alternative pre-mRNA splicing characteristic of metazoans are almost entirely unknown or uncertain. We describe here a novel family of splicing regulators present throughout metazoans. Specifically, we analyze two nematode (Caenorhabditis elegans) genes. One, CeSWAP, is a cognate of the suppressor-of-whiteapricot (DmSWAP) splicing regulator from the arthropod Drosophila. Our results define the ancient, conserved SWAP protein family whose members share a colinearly arrayed series of novel sequence motifs. Further, we describe evidence that the CeSWAP protein autoregulates its levels by feedback control of splicing of its own pre-mRNA analogously to the DmSWAP protein and as expected of a splicing regulator. The second nematode gene, Ceprp21, encodes an abundant nuclear cognate of the constitutive yeast splicing protein, prp21, on the basis of several lines of evidence. Our analysis defines prp21 as a second novel, ancient protein family. One of the motifs conserved in prp21 proteins–designated surp–is shared with SWAP proteins. Several lines of evidence indicate that both new families of surp-containing proteins act at the same (or very similar) step in early prespliceosome assembly. We discuss implications of our results for regulated metazoan pre-mRNA splicing.


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