Alternative splicing of the human estrogen receptor alpha primary transcript: mechanisms of exon skipping - PubMed (original) (raw)
Affiliations
- PMID: 12883652
Alternative splicing of the human estrogen receptor alpha primary transcript: mechanisms of exon skipping
Paola Ferro et al. Int J Mol Med. 2003 Sep.
Abstract
The 1785 nucleotides of the coding region of the estrogen receptor alpha (ER-alpha) 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-alpha 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.
Similar articles
- Familial adenomatous polyposis: aberrant splicing due to missense or silent mutations in the APC gene.
Aretz S, Uhlhaas S, Sun Y, Pagenstecher C, Mangold E, Caspari R, Möslein G, Schulmann K, Propping P, Friedl W. Aretz S, et al. Hum Mutat. 2004 Nov;24(5):370-80. doi: 10.1002/humu.20087. Hum Mutat. 2004. PMID: 15459959 - In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G-->A mutations in introns of the dystrophin gene.
Habara Y, Takeshima Y, Awano H, Okizuka Y, Zhang Z, Saiki K, Yagi M, Matsuo M. Habara Y, et al. J Med Genet. 2009 Aug;46(8):542-7. doi: 10.1136/jmg.2008.061259. Epub 2008 Nov 10. J Med Genet. 2009. PMID: 19001018 - Target selection for antisense oligonucleotide induced exon skipping in the dystrophin gene.
Errington SJ, Mann CJ, Fletcher S, Wilton SD. Errington SJ, et al. J Gene Med. 2003 Jun;5(6):518-27. doi: 10.1002/jgm.361. J Gene Med. 2003. PMID: 12797117 - Alternative splicing of mutually exclusive exons--a review.
Pohl M, Bortfeldt RH, Grützmann K, Schuster S. Pohl M, et al. Biosystems. 2013 Oct;114(1):31-8. doi: 10.1016/j.biosystems.2013.07.003. Epub 2013 Jul 11. Biosystems. 2013. PMID: 23850531 Review. - Bioinformatics and mutations leading to exon skipping.
Desmet FO, Béroud C. Desmet FO, et al. Methods Mol Biol. 2012;867:17-35. doi: 10.1007/978-1-61779-767-5_2. Methods Mol Biol. 2012. PMID: 22454052 Review.
Cited by
- Use of Attribute Driven Incremental Discretization and Logic Learning Machine to build a prognostic classifier for neuroblastoma patients.
Cangelosi D, Muselli M, Parodi S, Blengio F, Becherini P, Versteeg R, Conte M, Varesio L. Cangelosi D, et al. BMC Bioinformatics. 2014;15 Suppl 5(Suppl 5):S4. doi: 10.1186/1471-2105-15-S5-S4. Epub 2014 May 6. BMC Bioinformatics. 2014. PMID: 25078098 Free PMC article. - Exogenous hormonal regulation in breast cancer cells by phytoestrogens and endocrine disruptors.
Albini A, Rosano C, Angelini G, Amaro A, Esposito AI, Maramotti S, Noonan DM, Pfeffer U. Albini A, et al. Curr Med Chem. 2014;21(9):1129-45. doi: 10.2174/09298673113206660291. Curr Med Chem. 2014. PMID: 24304271 Free PMC article. - Logic Learning Machine creates explicit and stable rules stratifying neuroblastoma patients.
Cangelosi D, Blengio F, Versteeg R, Eggert A, Garaventa A, Gambini C, Conte M, Eva A, Muselli M, Varesio L. Cangelosi D, et al. BMC Bioinformatics. 2013;14 Suppl 7(Suppl 7):S12. doi: 10.1186/1471-2105-14-S7-S12. Epub 2013 Apr 22. BMC Bioinformatics. 2013. PMID: 23815266 Free PMC article. - Analysis of estrogen receptor isoforms and variants in breast cancer cell lines.
Al-Bader M, Ford C, Al-Ayadhy B, Francis I. Al-Bader M, et al. Exp Ther Med. 2011 May;2(3):537-544. doi: 10.3892/etm.2011.226. Epub 2011 Mar 10. Exp Ther Med. 2011. PMID: 22977537 Free PMC article. - Estrogen receptors and the regulation of neural stress responses.
Handa RJ, Mani SK, Uht RM. Handa RJ, et al. Neuroendocrinology. 2012;96(2):111-8. doi: 10.1159/000338397. Epub 2012 Sep 14. Neuroendocrinology. 2012. PMID: 22538291 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials