RNA•DNA:DNA triplex formation by HIF1α-AS1 modulates individual base pair stabilities in the adrenomedullin DNA
Nina M Krause1, Julia Wirmer-Bartoschek1, Christian Richter1
1Center for Biomolecular Magnetic Resonance (BMRZ), Institute for Organic Chemistry and Chemical Biology, Johann Wolfgang Goethe University, Frankfurt am Main 60438, Germany.
Abstract:
Long noncoding RNAs (lncRNAs) play key roles in gene regulation. One potential regulation mechanism involves the formation of RNA•DNA:DNA triplexes. In these triplexes, the lncRNA binds in the major groove of a target DNA via Hoogsteen base pair formation. Here, we investigated the impact of the underlying RNA binding on the stability of the DNA duplex target to gain insights into the triplex stability at base pair resolution with an isolated triplex system. Quantification of the temperature-dependent exchange of imino hydrogen atoms with solvent of the target DNA duplex allows determination of the changes in the stability of individual DNA duplex base pairs upon triplex formation. The data shown here investigates an antiparallel triplex, formed between the lncRNA hypoxia-inducible factor 1-α antisense RNA 1 (HIF1α-AS1) and the DNA target adrenomedullin (ADM), important in cardiovascular diseases. Triplex formation alters DNA structure and stability by affecting both hydrogen bonding strength and nucleobase-stacking interactions. These thermodynamic insights support bioinformatic methods to predict triplex stability and enhance our understanding of RNA•DNA:DNA triplex formation.
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