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

摘要: The Steroid Receptor RNA Activator 1 (SRA1) has originally been described as a noncoding specifically activating steroid receptor transcriptional activity. We have, however, identified, in human breast tissue, exon- extended SRA1 isoforms containing two initiating AUG codons and encoding protein we called SRAP. recently reported decreased estrogen activity cancer cells overexpressing SRAP, suggesting antagonist roles played by appears to be the first example of molecule active both at level. No data are currently available regarding mechanisms possibly involved generation coding functional RNAs. Using 5'-Rapid Amplification cDNA Extremities (5'-RACE), have herein identified several putative transcription initiation sites surrounding second methionine codon used generate transcripts. In process, also an alternatively spliced transcript still intron-1 sequence. targeted RT-PCR approaches, confirmed presence cell lines RNAs full well partial sequence established that relative proportion these varied within lines. "minigene" strategy, showed artificial Interestingly, splicing pattern minigene products parallels one endogenous Altogether, our suggest primary genomic around is sufficient lead differential this intron. propose alternative mechanism regulate balance between