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SRA: Steroid receptor RNA Activator
Bifunctional gene, active as an RNA and encodes a conserved protein SRAP (reviewed in Leygue (2007)). SRA has a large number of isoforms, most of which share a central core region. Only some isoforms are also able to encode the SRAP protein, and differential splicing may be one mechanism of generating coding and noncoding isoforms of SRA (Hube (2006)) (reviewed in Leygue (2007)). A number of functional motifs, with predicted secondary structures, are required for SRA RNA function (Lanz (2002)).
Forms ribonucleoprotein complexes with a number of nuclear receptors (including many steroid hormone receptors) generally acting to stimulate transcriptional activation (Lanz (1999), Leygue (2007)). Interacts either directly or through a complex with a number of other co-activator and repressor proteins, such as SRC-1, Sharp, SLIRP and p68 and p72 RNA helicases. SRA has been suggested to act as a scaffold for these complexes (reviewed in Leygue (2007)). Transgenic expression of SRA in vivo caused hyperplasia and morphological abnormalities in steroid hormone responsive tissues. Hyperplasia was accompanied by higher apoptosis however and expression of SRA did not lead to tumourigenesis (Lanz (2003)). Associated with cardiomyopathy in humans, a role in heart development was validated in zebrafish but it's unclear if SRAP or SRA or both is responsible (Friedrichs (2009)). SRA activity is regulated by pseudouridylation (Zhao (2004), Zhao (2007)).
Expressed in a wide range of tissues, some isoforms appear to have tissue specific expression (Lanz (1999), Lanz (2003)). Up-regulated in tumours of steroid hormone responsive tissues ie: breast, uterus and ovary compared to matched normal tissue (Murphy (2000), Lanz (2003)). Found in the nucleus and the cytoplasm (Lanz (2003), Zhao (2007)).
Some isoforms of SRA encode a conserved protein product SRAP, which is also expressed in normal tissues and breast cancer (Emberley (2003), Chooniedass-Kothari (2004), Chooniedass-Kothari (2006)). Studies show SRAP can also regulate the activity of nuclear receptors and bind to promoter regions regulated by nuclear receptors, suggesting functional similarities between SRA RNA and SRAP (Chooniedass-Kothari (2010), Chooniedass-Kothari (2010)). Leygue (2007) provides a useful review of the literature.
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