Alternative splicing of the human estrogen receptor α primary transcript: Mechanisms of exon skipping

  • Authors:
    • Paola Ferro
    • Alessandra Forlani
    • Marco Muselli
    • Ulrich Pfeffer
  • View Affiliations

  • Published online on: September 1, 2003     https://doi.org/10.3892/ijmm.12.3.355
  • Pages: 355-363
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The 1785 nucleotides of the coding region of the estrogen receptor α (ER-α) are dispersed over a region of more than 300,000 nucleotides in the primary transcript. Splicing of this precursor RNA frequently leads to variants lacking one or more exons that have been associated to breast cancer progression. The most frequent splice variant lacks exon 4 and is expressed in the human mammary carcinoma cell line MCF-7 at a level similar to that of the full-length messenger. The in silico analysis of ER-α splice sites by Hamming clustering, a self learning method trained on more than 28,000 experimentally proved splice sites, reveals high relevance for the 5' and 3' splice sites of exon 4. The splicing analysis of transfected mini-gene constructs containing drastically shortened introns excludes that weak splice sites, intron or exon lengths or splice enhancers are responsible for exon skipping. Exon 6 is never skipped in MCF-7 cells but is spliced out from mini-gene derived primary transcripts if inserted between exons 3 and 5 instead of exon 4. As a consequence, it appears that a particular splice site affinity of exon 3 donor (5' splice site) and exon 5 acceptor sites (3' splice site) is responsible for skipping of the exon in between.

Related Articles

Journal Cover

September 2003
Volume 12 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ferro P, Forlani A, Muselli M and Pfeffer U: Alternative splicing of the human estrogen receptor α primary transcript: Mechanisms of exon skipping. Int J Mol Med 12: 355-363, 2003
APA
Ferro, P., Forlani, A., Muselli, M., & Pfeffer, U. (2003). Alternative splicing of the human estrogen receptor α primary transcript: Mechanisms of exon skipping. International Journal of Molecular Medicine, 12, 355-363. https://doi.org/10.3892/ijmm.12.3.355
MLA
Ferro, P., Forlani, A., Muselli, M., Pfeffer, U."Alternative splicing of the human estrogen receptor α primary transcript: Mechanisms of exon skipping". International Journal of Molecular Medicine 12.3 (2003): 355-363.
Chicago
Ferro, P., Forlani, A., Muselli, M., Pfeffer, U."Alternative splicing of the human estrogen receptor α primary transcript: Mechanisms of exon skipping". International Journal of Molecular Medicine 12, no. 3 (2003): 355-363. https://doi.org/10.3892/ijmm.12.3.355