Steroid receptor RNA activator bi-faceted genetic system: Heads or Tails?

The Steroid Receptor RNA Activator (SRA) was first identified by Lanz et al. in 1999 as a functional non-coding RNA able to co-activate steroid nuclear receptors. Since this incipient study, our understanding of SRA as a broader co-regulator of nuclear receptors as well as other transcription factors has greatly expanded. Accumulated data has now revealed the diverse roles played by this transcript in both normal biological processes such as myogenesis and adipogenesis, as well as in mechanisms underlying diseases including cardio-myopathies and cancers. Remarkably, as early as 2000, SRA isoforms were identified that were also able to code for a protein now referred to as the Steroid Receptor RNA Activator Protein (SRAP). SRA and SRAP now define a very intriguing bi-faceted genetic system, where both RNA and protein products of the same gene play specific and sometime overlapping roles in cell biology. Due to its initial molecular characterization as an RNA, most reports have in the last ten years focused on the non-coding part of this twosome. As such, only a handful of laboratories have investigated the molecular and biological roles played by SRAP. The scope of this review is to summarize and discuss our current knowledge of the molecular features and functions specifically attributable to the coding nature of the bi-faceted products of the SRA1 gene. ► The SRA-1 gene produces both functional coding and non-coding transcripts. ► SRAP has two evolutionarily conserved domains. ► SRAP can act as both a transcriptional co-activator as well as co-repressor. ► SRA RNA and SRAP are involved in similar molecular pathways. ► The balance of coding and non-coding transcripts occurs through alternative splicing.