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Transcription regulation by RNA-induced structural strain in duplex DNA.
Aura Cencini1, Graziano Rilievo1, Alessandro Cecconello1,2
1Department of Comparative Biomedicine and Food Science (BCA), University of Padova, Campus Agripolis, viale dell'Università 16, 35020 Legnaro (PD), Italy.
Nucleic Acids Research
|May 22, 2025
Summary
Long non-coding RNAs (lncRNAs) can regulate gene expression by forming RNA-DNA triplexes. This study reveals how these triplexes modulate transcription rates in bacterial systems, offering insights into gene regulation mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are key regulators of gene expression.
- lncRNAs are hypothesized to interact with DNA, forming triple helices, but direct experimental evidence for their role in transcription modulation is limited.
Purpose of the Study:
- To investigate the mechanism by which RNA-DNA triplexes regulate transcription rates.
- To explore the potential of these triplexes in synthetic biology for controlling gene expression.
Main Methods:
- Identification and in vitro characterization of triplex-associated sequences in bacterial promoters.
- Application of synthetic biology techniques to verify transcription and translation control.
- Computational modeling of the triplex-promoter complex.
Main Results:
- Demonstrated that hybrid RNA-DNA triplexes can enhance or inhibit transcription rates in designed bacterial promoter architectures.
- Identified a mechanism where DNA distortion within the triplex assembly leads to transcription enhancement.
- Successfully used triplex formation to control transcription and translation.
Conclusions:
- RNA-DNA triplexes represent a novel mechanism for gene transcription regulation.
- This mechanism, observed in bacteria, may be conserved and play a significant role in complex organisms like mammals for chromatin modulation.
- Findings open new avenues for understanding non-coding RNA function and developing synthetic gene control systems.
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