A method for RNA structure prediction shows evidence for structure in lncRNAs

Riccardo Delli ponti; Alexandros Armaos; Stefanie Marti; Gian Gaetano Tartaglia

To further investigate the secondary structure of HOTAIR, we studied the structural conservation of the D4 domain (Supplementary Figure 10) . As opposed to D2, D4 is predicted by CROSS to be poorly structured ( Figure 5B ). Searching for orangutan D4 within all human lncRNAs yields HOTAIR as the best match (structural distance 0.023; p-value < 10 -6 ) and the reported sequence position shows a sizeable overlap with the D4 domain in human HOTAIR (predicted coordinates: 1650-2291; overlap of 79%; Figure 7A ). By contrast, when searching for mouse D4 within all human lncRNAs, HOTAIR shows poor ranking (1849 th ; structural distance 0.104; p-value = 0.061), which indicates little structural homology between human and mouse ( Figure Table 3) to identify structurally similar domains. We found that coronavirus HKU and Simian-Human immunodeficiency SIV have the most significant matches with HIV (structural distance 0.078, p-value < 10 -6 for SIV; structural distance 0.093, p-value < 10 -4 for HKU). This finding is particularly relevant since SIV and HIV share many similarities in terms of pathogenicity and evolution [29] . Indeed, previous studies already reported a similarity in terms of secondary structure between HIV and SIV that is not explained by sequence similarity [30] .