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.
RNA (New York, N.Y.)
|May 5, 2026
Summary
Long non-coding RNAs (lncRNAs) can regulate genes by forming RNA•DNA:DNA triplexes. This study quantifies how lncRNA binding affects DNA duplex stability, revealing insights into triplex stability and gene regulation mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Long non-coding RNAs (lncRNAs) are crucial regulators of gene expression.
- RNA•DNA:DNA triplexes represent a significant mechanism for lncRNA-mediated gene regulation.
- These triplexes form when lncRNAs bind to DNA major grooves via Hoogsteen base pairing.
Purpose of the Study:
- To investigate the impact of RNA binding on DNA duplex stability at base pair resolution.
- To gain insights into the thermodynamic stability of RNA•DNA:DNA triplexes.
- To analyze the specific lncRNA HIF1α-AS1 and its DNA target ADM, relevant to cardiovascular diseases.
Main Methods:
- Quantification of temperature-dependent imino hydrogen exchange with solvent in the DNA duplex.
- Determination of individual DNA duplex base pair stability changes upon triplex formation.
- Investigation of an antiparallel triplex formed between HIF1α-AS1 and ADM DNA.
Main Results:
- Triplex formation significantly alters DNA duplex structure and stability.
- Changes in stability are attributed to modifications in hydrogen bonding strength and nucleobase-stacking interactions.
- Thermodynamic data provides base-pair resolution insights into triplex stability.
Conclusions:
- RNA•DNA:DNA triplex formation impacts DNA stability through altered base pairing and stacking.
- These findings support the development of bioinformatic tools for predicting triplex stability.
- Enhanced understanding of triplex formation contributes to knowledge of lncRNA gene regulation.
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