A high-throughput approach to profile RNA structure

Delli Ponti, Riccardo; Marti, Stefanie; Armaos, Alexandros; Tartaglia, Gian Gaetano

Due to the complexity of the configuration space, the structural profile of sequences >1 000-1 500 nucleotides is extremely difficult to predict with thermodynamic approaches (22) , which makes CROSS a valid alternative to study long non-coding RNAs (23) . To illustrate CROSS performances on large RNAs, we predicted the structural profile of murine Xist non-coding RNA (17 900 nt) using the consensus of our five models (Materials and Methods: Consensus models; Figure 7A ). Xist was analyzed using DMS probing (16) , an independent technique not used in the training of Figure S10 ). Although the method slightly overestimates the structural content of Rep E, it is able to accurately predict its profile (correlation of 0.63, Supplementary Figure S10 ). While the sequences of Rep A and B are conserved across species and show a high degree of structural content, the 3 region of Xist is variable (24) and predicted by CROSS to be more single-stranded.