Assuming a Coactivating Structure

Abstract

Steroid hormone receptors interact with various coactivators and corepressors to control gene expression. One of the coactivators has been reported to be an RNA called steroid receptor RNA activator (SRA). Lanz et al. used secondary structure prediction software to identify structures adopted by SRA and then created silent mutations--ones that would not alter any putative protein product--that would disrupt the predicted RNA structures. In transfected cells, these mutated SRAs had less coactivator activity toward progesterone receptor-mediated gene expression. Deletion analysis suggested that there was not a short definable sequence responsible for SRA coactivator activity, which is consistent with a complex secondary structure that requires that sequences distributed throughout the RNA are necessary for activity. Of the 11 predicted structures, mutations that disrupted 5 of the structures decreased coactivation of gene expression. These experiments firmly support the concept that it is the RNA and not an encoded protein that is responsible for SRA activity. Thus, in addition to protein partners, steroid receptor activity is modulated by RNA regulatory molecules as well. R. B. Lanz, B. Razani. A. D. Goldberg, B. W. O'Malley, Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc. Natl. Acad. Sci. U.S.A. 99 , 16081-16086 (2002). [Abstract] [Full Text]