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PNAS 99 (25): 16081-16086

Copyright © 2002 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA)

Rainer B. Lanz, Bahram Razani, Aaron D. Goldberg, and Bert W. O'Malley*

Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030

Contributed by Bert W. O'Malley

Accepted for publication September 20, 2002.

Abstract: Steroid receptor RNA activator (SRA) is an RNA transcript that functions as a eukaryotic transcriptional coactivator for steroid hormone receptors. We report here the isolation and functional characterization of distinct RNA substructures within the SRA molecule that constitute its coactivation function. We used comparative sequence analysis and free energy calculations to systematically study SRA RNA subdomains for identification of structured regions and base pairings, and we used site-directed mutagenesis to assess their functional consequences. Together with genetic deletion analysis, this approach identified six RNA motifs in SRA important for coactivation. Because all nucleotide changes in the mutants that disrupted SRA function were silent mutations presumed not to alter deduced encoded amino acid sequence, our analysis provides strong evidence that SRA-mediated coactivation is executed by distinct RNA motifs and not by an encoded protein.


* To whom correspondence should be addressed. E-mail: berto{at}bcm.tmc.edu.


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