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Alternative Splicing of the First Intron of the Steroid Receptor RNA Activator (SRA) Participates in the Generation of Coding and Noncoding RNA Isoforms in Breast Cancer Cell Lines

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dc.contributor.author Hube, F.
dc.contributor.author Guo, J.
dc.contributor.author Chooniedass-Kothari, S.
dc.contributor.author Cooper, C.
dc.contributor.author Hamedani, M. K.
dc.contributor.author Dibrov, A. A.
dc.contributor.author Blanchard, A. A. A.
dc.contributor.author Wang, X.
dc.contributor.author Deng, G.
dc.contributor.author Myal, Y.
dc.contributor.author Leygue, E.
dc.date.accessioned 2010-01-29T19:12:08Z
dc.date.available 2010-01-29T19:12:08Z
dc.date.issued 2006-07
dc.identifier.citation Hube, F., Guo, J., Chooniedass-Kothari, S., Cooper, C., Hamedani, M.K., Dibrov, A.A., Blanchard, A.A., Wang, X., Deng, G., Myal, Y. & Leygue, E. Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA isoforms in breast cancer cell lines. DNA Cell Biol 25, 418-428 (2006). en_US
dc.identifier.uri http://hdl.handle.net/1807.1/831
dc.description Reproduced by generous permission of the publisher. en_US
dc.description http://www.liebertpub.com/ en_US
dc.description.abstract The Steroid Receptor RNA Activator 1 (SRA1) has originally been described as a noncoding RNA specifically activating steroid receptor transcriptional activity. We have, however, identified, in human breast tissue, exon- 1 extended SRA1 isoforms containing two initiating AUG codons and encoding a protein we called SRAP. We recently reported a decreased estrogen receptor activity in breast cancer cells overexpressing SRAP, suggesting antagonist roles played by SRA1 RNA and SRAP. SRA1 appears to be the first example of a molecule active both at the RNA and at the protein level. No data are currently available regarding the mechanisms possibly involved in the generation of coding and noncoding functional SRA1 RNAs. Using 5 -Rapid Amplification of cDNA Extremities (5 -RACE), we have herein identified several putative transcription initiation sites surrounding the second methionine codon and used to generate coding SRA1 transcripts. In the process, we also identified an alternatively spliced noncoding SRA1 transcript still containing an intron-1 sequence. Using targeted RT-PCR approaches, we confirmed the presence in breast cancer cell lines of SRA1 RNAs containing a full as well as a partial intron-1 sequence and established that the relative proportion of these RNAs varied within breast cancer cell lines. Using a “minigene” strategy, we also showed that artificial RNAs containing the SRA1 intron-1 sequence are alternatively spliced in breast cancer cell lines. Interestingly, the splicing pattern of the minigene products parallels the one of the endogenous SRA1 transcripts. Altogether, our data suggest that the primary genomic sequence in and around intron-1 is sufficient to lead to a differential splicing of this intron. We propose that alternative splicing of intron-1 is one mechanism used by breast cancer cells to regulate the balance between coding and functional noncoding SRA1 RNAs. en_US
dc.description.provenance Submitted by Kelly Lee (klee@cbcra.ca) on 2010-01-29T19:12:08Z No. of bitstreams: 1 Leygue.pdf: 1620693 bytes, checksum: c74ffb52772f6411d334e6fd53b70b36 (MD5) en
dc.description.provenance Made available in DSpace on 2010-01-29T19:12:08Z (GMT). No. of bitstreams: 1 Leygue.pdf: 1620693 bytes, checksum: c74ffb52772f6411d334e6fd53b70b36 (MD5) Previous issue date: 2006-07 en
dc.language.iso en en_US
dc.publisher Mary Ann Liebert, Inc. en_US
dc.title Alternative Splicing of the First Intron of the Steroid Receptor RNA Activator (SRA) Participates in the Generation of Coding and Noncoding RNA Isoforms in Breast Cancer Cell Lines en_US
dc.type Article en_US

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