Three-dimensional computational modeling of the TLC1 Est1-arm conserved region. (A) TLC1 Est1-arm conserved region secondary structure, with sub-elements colored. (Blue) 5′ side of the internal loop, (green) 3′ side of internal loop, (orange) apical hairpin, (yellow) hinge-hairpin, and (red) bulge. Open circles indicate the potential A–U pairs across the internal loop. (B) Three-dimensional structure prediction by RNAComposer of the Est1-arm conserved region with unpaired internal loop. Inset shows internal loop secondary structure, with the three unpaired A and U residues boxed. The structure of the entire 193-nt Est1 arm (nucleotides 508–700) was modeled. (C) Three A–U base pairs in the internal loop lead to prediction of a very different tertiary structure with coaxially stacked RNA helices. Inset shows the corresponding secondary structure, with the A–U pairs boxed.