RESUMO
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.
Assuntos
RNA não Traduzido/genética , Processamento Alternativo , Sequência de Aminoácidos , Animais , Regulação da Expressão Gênica , Humanos , Redes e Vias Metabólicas/genética , Camundongos , Conformação Molecular , Dados de Sequência Molecular , Fases de Leitura Aberta/genética , Filogenia , Isoformas de RNA/genética , RNA Longo não Codificante , RNA não Traduzido/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismoRESUMO
Products of the steroid receptor RNA activator (SRA1) gene have the unusual property to function both at the RNA and the protein levels. SRA-RNA has long been known to increase the activity of multiple nuclear receptors. It has more recently been proposed than steroid receptor RNA activator protein (SRAP) also modulates steroid receptors activity. Herein, we show for the first time that SRAP physically interacts with multiple transcription factors and is recruited to specific promoter regions. Artificially recruiting SRAP to the promoter of a luciferase reporter gene under the control of the strong transcriptional activator VP16 leads to a decrease in transcription. Altogether we propose that SRAP could be a new transcriptional regulator, able to function as a repressor through direct association with promoters.
Assuntos
Proteínas/metabolismo , RNA não Traduzido/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Transporte/metabolismo , Humanos , RNA/metabolismo , RNA Longo não Codificante , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismoRESUMO
The steroid receptor RNA activator gene (SRA1) encodes for a functional RNA (SRA) as well as a protein (SRAP). While several groups reported on SRA-RNA mechanism of action, SRAP exact function remains to be elucidated, mainly due to a lack of studies investigating the function of the protein independently of its RNA counterpart. Using two independent models to examine its specific functions, SRAP was found to enhance estrogen receptor alpha activity in a ligand and response-element dependent manner. Our data therefore suggest that both transcript and protein products of the SRA1 gene co-modulate the transcriptional activity of steroid receptors.
