title: Structural architecture of the human long non-coding RNA, steroid receptor RNA activator.
abstract: While functional roles of several long non-coding RNAs (lncRNAs) have been determined, the molecular mechanisms are not well understood. Here, we report the first experimentally derived secondary structure of a human lncRNA, the steroid receptor RNA activator (SRA), 0.87 kB in size. The SRA RNA is a non-coding RNA that coactivates several human sex hormone receptors and is strongly associated with breast cancer. Coding isoforms of SRA are also expressed to produce proteins, making the SRA gene a unique bifunctional system. Our experimental findings (SHAPE, in-line, DMS and RNase V1 probing) reveal that this lncRNA has a complex structural organization, consisting of four domains, with a variety of secondary structure elements. We examine the coevolution of the SRA gene at the RNA structure and protein structure levels using comparative sequence analysis across vertebrates. Rapid evolutionary stabilization of RNA structure, combined with frame-disrupting mutations in conserved regions, suggests that evolutionary pressure preserves the RNA structural core rather than its translational product. We perform similar experiments on alternatively spliced SRA isoforms to assess their structural features.
authors.affiliation: Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Novikova
authors.forename: Scott P
authors.initials: SP
authors.lastname: Hennelly
authors.forename: Karissa Y
authors.initials: KY
authors.lastname: Sanbonmatsu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000737:chemistry*; D012260:Ribonucleases; D016415:Sequence Alignment
chemical_list: D002352:Carrier Proteins; D009711:Nucleotides; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C405423:steroid receptor RNA activator; C548898:steroid receptor RNA activator, human; D012260:Ribonucleases