title: 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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Hewei
authors.initials: H
authors.lastname: Zheng
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Lu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. Electronic address: lixia@hrbmu.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D003198:Computer Simulation; D030541:Databases, Genetic; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D000072417:Protein Domains; D062085:RNA, Long Noncoding / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D014157:Transcription Factors
keywords: Coordinate regulation of transcription; HOTAIR; LncRNA secondary structure; Pan-cancer relevant; RNA structurome; Thermodynamic model