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Nucleic Acids Research, 1994, Vol. 22, No. 6 1018-1022
© 1994


RNA

A novel bipartite splicing enhancer modulates the differential processing of the human fibronectin EDA exon

M. Caputi, G. Casari+, S. Guenzi§, R. Tagliabue, A. Sidoli§, C.A. Melo and F.E. Baralle*

International Centre for Genetic Engineering and Biotechnology-UNIDO Padriciano 99, Area Science Park, 34012 Trieste, Italy

*To whom correspondence should be addressed

Received December 17, 1993. Accepted February 16, 1994.

EDA is a facultative type III homology of human fibronectin encoded by an alternative spliced exon. The EDA+ and EDA- mRNA forms show a cell type specific distribution with their relative proportion varying during development, aging and oncogenlc transformation. We have previously demonstrated that an 81 bp nucleotide sequence within the exon itself is essential for differential RNA processing. Fine mapping of cis acting elements within this region has been carried out to Identify possible target sites for the modulation of alternative splicing. There are at least two short nucleotide sequences involved. Element A (GAAGAAGA) is a positive modulator for the recognition of the exon, Its deletion results in constitutive exclusion of the EDA exon. Element B (CAAGG) is a negative modulator for exon recognition, its deletion results in constitutive inclusion of the EDA exon. This bipartite structure of the splicing enhancer is a novel feature of the mammalian exons.


+Present addresses: Prassis-Sigma Tau Research Institute. Via Forlanini 3, 20019 Settimo Milanese, Milan

§Present addresses: Department of Sciences and Biomcdical Technologies, S. Raffaele Hospital. Via Olgettina 60. 20132 Milan, Italy


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