An exon-biased biophysical approach and NMR spectroscopy define the secondary structure of a conserved helical element within the HOTAIR long non-coding RNA
| Autor: | Alexander Hirschi, Ainur Abzhanova, Nicholas J. Reiter |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
RNA Folding
0303 health sciences Magnetic Resonance Spectroscopy Sequence analysis Chemistry Base pair 030302 biochemistry & molecular biology RNA HOTAIR Exons Computational biology Non-coding RNA Article Nucleic acid secondary structure 03 medical and health sciences Exon Structural Biology Humans Nucleic Acid Conformation RNA Long Noncoding Ultracentrifugation Protein secondary structure 030304 developmental biology |
| Zdroj: | J Struct Biol |
| ISSN: | 1047-8477 |
| DOI: | 10.1016/j.jsb.2021.107728 |
| Popis: | HOTAIR is a large, multi-exon spliced non-coding RNA proposed to function as a molecular scaffold and competes with chromatin to bind to histone modification enzymes. Previous sequence analysis and biochemical experiments identified potential conserved regions and characterized the full length HOTAIR secondary structure. Here, we examine the thermodynamic folding properties and structural propensity of the individual exonic regions of HOTAIR using an array of biophysical methods and NMR spectroscopy. We demonstrate that different exons of HOTAIR contain variable degrees of heterogeneity, and identify one exonic region, exon 4, that adopts a stable and compact fold under low magnesium concentrations. Close agreement of NMR spectroscopy and chemical probing unambiguously confirm conserved base pair interactions within the structural element, termed helix 10 of exon 4, located within domain I of human HOTAIR. This combined exon-biased and integrated biophysical approach introduces a new strategy to examine conformational heterogeneity in lncRNAs and emphasizes NMR as a key method to validate base pair interactions and corroborate large RNA secondary structures. |
| Databáze: | OpenAIRE |
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