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Molecular and Cellular Biology, April 1999, p. 2657-2671, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Regulation of Fibronectin EDA Exon Alternative Splicing: Possible Role of RNA Secondary Structure for Enhancer Display

Andrés F. Muro, Massimo Caputi,dagger Rajalakshmi Pariyarath,Dagger Franco Pagani, Emanuele Buratti, and Francisco E. Baralle*

International Centre for Genetic Engineering and Biotechnology, I-34012 Trieste, Italy

Received 3 August 1998/Returned for modification 14 September 1998/Accepted 28 December 1998

The fibronectin primary transcript undergoes alternative splicing in three noncoordinated sites: the cassette-type EDA and EDB exons and the more complex IIICS region. We have shown previously that an 81-nucleotide region within the EDA exon is necessary for exon recognition and that this region contains at least two splicing-regulatory elements: a polypurinic enhancer (exonic splicing enhancer [ESE]) and a nearby silencer element (exonic splicing silencer [ESS]). Here, we have analyzed the function of both elements in different cell types. We have mapped the ESS to the nucleotide level, showing that a single base change is sufficient to abolish its function. Testing of the ESE and ESS elements in heterologous exons, individually or as part of the complete EDA regulatory region, showed that only the ESE element is active in different contexts. Functional studies coupled to secondary-structure enzymatic analysis of the EDA exon sequence variants suggest that the role of the ESS element may be exclusively to ensure the proper RNA conformation and raise the possibility that the display of the ESE element in a loop position may represent a significant feature of the exon splicing-regulatory region.

* Corresponding author. Mailing address: ICGEB, Padriciano 99, I-34012 Trieste, Italy. Phone: (39)-040-3757337. Fax: (39)-040-3757361. E-mail: baralle{at}icgeb.trieste.it.

dagger Present address: Department of Biology, Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA 95064.

Dagger Present address: Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029.

Molecular and Cellular Biology, April 1999, p. 2657-2671, Vol. 19, No. 4
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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