This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Domenjoud, L Articles by Jacob, M Search for Related Content PubMed PubMed Citation Articles by Domenjoud, L Articles by Jacob, M

 Previous Article  |  Next Article 

Mol Cell Biol. 1991 September; 11(9): 4581-4590

Identification of a specific exon sequence that is a major determinant in the selection between a natural and a cryptic 5' splice site.

Laboratoire de Génétique Moléculaire des Eucaryotes du Centre National de la Recherche Scientifique, Unité 184, Faculté de Médecine, Strasbourg, France.

ABSTRACT

The first intron of the early region 3 from adenovirus type 2 contains a cryptic 5' splice site, Dcr1, 74 nucleotides downstream from the natural site D1. The cryptic site can be activated when the natural site is inactivated by mutagenesis. To investigate the basis for selection between a natural and a cryptic 5' splice site, we searched for cis-acting elements responsible for the exclusive selection of the natural site. We show that both the relative intrinsic strength of the sites and the sequence context affect the selection. A 120-nucleotide segment located at the 3' end of exon 1 enhances splicing at the proximal site D1; in its absence the two sites are used according to their strength. Thus, three cis-acting elements are involved in the silencing of the cryptic site: the sequence of D1, the sequence of Dcr1, and an upstream exonic sequence. We show that the exonic element folds, in solution, into a 113-nucleotide-long stem-loop structure. We propose that this potential stem-loop structure which is located 6 nucleotides upstream of the exon 1-intron junction is responsible for the preferential use of the natural 5' splice site.

This article has been cited by other articles:

• Singh, N. N., Singh, R. N., Androphy, E. J. (2007). Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes. Nucleic Acids Res 35: 371-389 [Abstract] [Full Text]  
• Buratti, E., Baralle, M., Baralle, F. E. (2006). Defective splicing, disease and therapy: searching for master checkpoints in exon definition. Nucleic Acids Res 34: 3494-3510 [Abstract] [Full Text]  
• Spena, S., Tenchini, M. L., Buratti, E. (2006). Cryptic splice site usage in exon 7 of the human fibrinogen B{beta}-chain gene is regulated by a naturally silent SF2/ASF binding site within this exon. RNA 12: 948-958 [Abstract] [Full Text]  
• Jones, R. B., Carstens, R. P., Luo, Y., McKeehan, W. L. (2001). 5'- and 3'-terminal nucleotides in the FGFR2 ISAR splicing element core have overlapping roles in exon IIIb activation and exon IIIc repression. Nucleic Acids Res 29: 3557-3565 [Abstract] [Full Text]  
• Hutton, M. (2001). Missense and splice site mutations in tau associated with FTDP-17: Multiple pathogenic mechanisms. Neurology 56: S21-25 [Abstract] [Full Text]  
• Grover, A., Houlden, H., Baker, M., Adamson, J., Lewis, J., Prihar, G., Pickering-Brown, S., Duff, K., Hutton, M. (1999). 5' Splice Site Mutations in tau Associated with the Inherited Dementia FTDP-17 Affect a Stem-Loop Structure That Regulates Alternative Splicing of Exon 10. J. Biol. Chem. 274: 15134-15143 [Abstract] [Full Text]  
• Muro, A. F., Caputi, M., Pariyarath, R., Pagani, F., Buratti, E., Baralle, F. E. (1999). Regulation of Fibronectin EDA Exon Alternative Splicing: Possible Role of RNA Secondary Structure for Enhancer Display. Mol. Cell. Biol. 19: 2657-2671 [Abstract] [Full Text]  
• Lavigueur, A, La Branche, H, Kornblihtt, A R, Chabot, B (1993). A splicing enhancer in the human fibronectin alternate ED1 exon interacts with SR proteins and stimulates U2 snRNP binding.. Genes Dev. 7: 2405-2417 [Abstract]  
• Neel, H, Weil, D, Giansante, C, Dautry, F (1993). In vivo cooperation between introns during pre-mRNA processing.. Genes Dev. 7: 2194-2205 [Abstract]  
• Dietz, H., Valle, D, Francomano, C., Kendzior, R. Jr, Pyeritz, R., Cutting, G. (1993). The skipping of constitutive exons in vivo induced by nonsense mutations. Science 259: 680-683 [Abstract]