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Molecular and Cellular Biology, October 1998, p. 5930-5941, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Influence of Intron Length on Alternative Splicing of CD44

Martyn V. Bell,1,2 Alison E. Cowper,1 Marie-Paule Lefranc,2,dagger John I. Bell,1 and Gavin R. Screaton1,*

Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom,1 and Laboratoire d'Immunogénétique Moléculaire, Institut de Génétique Moléculaire CNRS UMR/G H5535, 34293 Montpellier Cedex 5, France,2

Received 17 February 1998/Returned for modification 15 April 1998/Accepted 9 July 1998

Although the splicing of transcripts from most eukaryotic genes occurs in a constitutive fashion, some genes can undergo a process of alternative splicing. This is a genetically economical process which allows a single gene to give rise to several protein isoforms by the inclusion or exclusion of sequences into or from the mature mRNA. CD44 provides a unique example; more than 1,000 possible isoforms can be produced by the inclusion or exclusion of a central tandem array of 10 alternatively spliced exons. Certain alternatively spliced exons have been ascribed specific functions; however, independent regulation of the inclusion or skipping of each of these exons would clearly demand an extremely complex regulatory network. Such a network would involve the interaction of many exon-specific trans-acting factors with the pre-mRNA. Therefore, to assess whether the exons are indeed independently regulated, we have examined the alternative exon content of a large number of individual CD44 cDNA isoforms. This analysis shows that the downstream alternatively spliced exons are favored over those lying upstream and that alternative exons are often included in blocks rather than singly. Using a novel in vivo alternative splicing assay, we show that intron length has a major influence upon the alternative splicing of CD44. We propose a kinetic model in which short introns may overcome the poor recognition of alternatively spliced exons. These observations suggest that for CD44, intron length has been exploited in the evolution of the genomic structure to enable tissue-specific patterns of splicing to be maintained.

* Corresponding author. Mailing address: Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. Phone: 01865 221609. Fax: 01865 222502. E-mail: GScreaton{at}worf.molbiol.ox.ac.uk.

dagger Present address: Laboratoire d'Immunogénétique Moléculaire, Universite Montpellier II, UPR CNRS 1142, IGH, 34396 Montpellier Cedex 5, France.

Molecular and Cellular Biology, October 1998, p. 5930-5941, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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