A steroid receptor coactivator, SRA, functions as an RNA and is present inan SRC-1 complex

Nuclear receptors play critical roles in the regulation of eukaryotic gene expression. We report the isolation and functional characterization of a no vel transcriptional coactivator, termed steroid receptor RNA activator (SRA ). SRA is selective for steroid hormone receptors and mediates transactivat ion via their aminoterminal activation function. We provide functional and mechanistic evidence that SRA acts as an RNA transcript; transfected SRA, u nlike other steroid receptor coregulators, functions in the presence of cyc loheximide, and SRA mutants containing multiple translational stop signals retain their ability to activate steroid receptor-dependent gene expression . Biochemical fractionation shows that SRA exists in distinct ribonucleopro tein complexes, one of which contains the nuclear receptor coactivator ster oid receptor coactivator 1. We suggest that SRA may act to confer functiona l specificity upon multiprotein complexes recruited by liganded receptors d uring transcriptional activation.