Figure 1. The first experimentally determined secondary structure of an intact lncRNA, to our knowledge. The steroid receptor RNA activator (SRA) lncRNA contains 4 subdomains, and 25 helices. The structure was determined using four methods of chemical (SHAPE, in-line, DMS) or enzymatic (RNase V1) probing. Covariance analysis based on multiple sequence alignment across vertebrates was used to help validate the structure. In SHAPE probing (selective 2’-hydroxyl acylation analyzed by primer extension), high reactivity corresponds to high mobility and low likelihood for base pairing; low reactivity corresponds to low mobility and high likelihood for base pairing. Orange, high SHAPE reactivity. Yellow, medium reactivity. Grey, low reactivity. Black, no reactivity. Insets: Red, SHAPE reactivity capillary electrophoresis trace for lncRNA. Green, raw blank trace.