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Mol Cell Biol, August 1998, p. 4924-4934, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Characterization of SRp46, a Novel Human SR Splicing Factor Encoded by a PR264/SC35 Retropseudogene

Johann Soret,1 dagger Renata Gattoni,2 Cécile Guyon,1 Alain Sureau,1 dagger Michel Popielarz,2 Erwann Le Rouzic,1 Stéphanie Dumon,1 Françoise Apiou,3 Bernard Dutrillaux,3 Hartmut Voss,4 Wilhelm Ansorge,4 James Stévenin,2 and Bernard Perbal1 5 *

Laboratoire d'Oncologie Virale et Moléculaire, INSERM U142, Bâtiment Kourilsky, Hôpital Saint-Antoine, Paris 75571 Cedex 12,1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 67404 Illkirch,2 Cytogénétique Moléculaire et Oncologie, CNRS-UMR147, Institut Curie, 75231 Paris,3 and Unité de Formation et de Recherche de Biochimie, Université Paris 7 (D. Diderot), 75005 Paris,5 France, and Biochemical Instrumentation, EMBL Heidelberg, 69117 Heidelberg, Germany4

Received 5 January 1998/Returned for modification 4 March 1998/Accepted 20 May 1998

The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with beta -globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.

* Corresponding author. Mailing address: UFR de Biochimie, Tour 42, Université Paris 7, D. Diderot, 2, Place Jussieu, 75005 Paris, France. Phone: 33 (0) 1 44 27 47 30. Fax: 33 (0) 1 30 64 18 65. E-mail: Bernard.Perbal{at}wanadoo.fr.

dagger Present address: CNRS-UMR146, Laboratoires R. Latarjet, Centre Universitaire, Orsay, France.

Mol Cell Biol, August 1998, p. 4924-4934, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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