RNA triplexes: from structural principles to biological and biotech applications

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• RNA's diverse biological functions depend on complex secondary and tertiary structures.
• RNA triplexes are crucial tertiary structure motifs found in pseudoknots and structured RNAs.
• These triplexes form via major or minor groove interactions within Watson-Crick base-paired stems.

Purpose of the Study:

• To provide an overview of naturally occurring RNA triplex structures.
• To summarize experimental methods for studying RNA triplexes.
• To review the development of triplex-forming oligonucleotides (TFOs) and peptide nucleic acids (PNAs) for biomedical applications.

Main Methods:

• Overview of naturally occurring RNA triplexes.
• Summary of experimental techniques for RNA triplex analysis.
• Review of TFOs and PNAs designed for specific RNA targeting.

Main Results:

• Major-groove triplexes form stable base triples (e.g., U·A-U, C(+)·G-C).
• Minor-groove triplexes, like A-minor motifs, are prevalent in large structured RNAs.
• Programmable TFOs and PNAs achieve enhanced binding affinity and specificity for RNA duplexes.

Conclusions:

• Targeting RNA duplexes via triplex formation has significant biomedical potential.
• Developed TFOs and PNAs effectively target specific RNAs, including those from HIV-1 and bacteria.
• These tools can inhibit critical RNA-protein interactions, offering therapeutic strategies.