Steroid receptor RNA activator (SRA) is a steroid receptor co-activator that has recently been shown to enhance estrogen induced transcriptional activity of estrogen receptors alpha and beta. SRA differs from the other steroid receptor co-activators, in that it was shown to function as a non-coding RNA molecule. The initial paper on SRA reported a lack of success in generating any in vitro or in vivo stable SRA protein. We have identified three SRA RNA isoforms sequences which, unlike the previously described non-coding RNA, have a longer 5’ end and encode a stable SRA protein. Through database analyses, we have also identified mRNA sequences of SRA for several classes of vertebrates. Analysis of the protein sequences showed that the SRA protein family members are similar in size and have two extremely well conserved regions. Using an SRA antibody targeted against the N-terminal conserved region of the protein and muscle extracts from different vertebrate species, we have detected in a protein band of similar size. In MCF-7 cells stably transfected with SRA cDNA, we unexpectedly found that ER alpha activity is reduced in the presence of estradiol compared to non-transfected cells. Therefore our results suggest a possible role for SRA protein that is distinct from the SRA RNA.

[Proc Amer Assoc Cancer Res, Volume 45, 2004]