Insight into HOTAIR structural features and functions as landing pads for transcription regulation proteins

Abstract LncRNAs fulfill a wide range of regulatory functions at almost every process of gene expression. While derived from secondary structural features, lncRNAs may function as landing pads for transcription factors (TFs). In this paper, we detected the global structural landscape of 20,338 lncRNAs by utilizing a free energy minimization (MFE) algorithm, and identified the interactions between lncRNAs and TFs to analyze molecular association induced by the lncRNA structure. The accessibility analysis of full sequences as well as potential TF-binding fragments shows a large percentage of structural flanking sequence around the TF binding sites. This investigations paid great attention to the high-order architecture of HOTAIR lncRNA, and identified two coincident modular domains covering fragments 171-410bp and 811-1520bp via RNA-TF association predicting and in-silico computation mining. Then, the structural domains were implied potential landing pads to recruit regulatory proteins (13 TFs) and mediated coordinate regulation of transcription. Pathways and diseases enrichment analysis illustrated that the interacted TFs are significantly Pan-cancer relevant which is consistent with the known function of HOTAIR. Overall, the in-depth understanding of HOTAIR structure provides the first glimpse of coordinate regulation driven by modular features. The detailed architectural context could yield broad biological insights and provides a framework for comprehending lncRNA structure-function interrelationships.