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Published on: October 7, 2025
A Programmable mRNA Platform for miRNA Detection via miRNA-mRNA2 Triplex-Mediated Ribosomal Frameshifting
Yanyu Chen1, Wanqi Zhao1, Huizhen Chen1,2
1School of Medicine, The Chinese University of Hong Kong (Shenzhen), Longgang, Shenzhen 518172, Guangdong, P. R. China.
ACS Synthetic Biology
|July 17, 2026
Summary
Scientists developed a programmable mRNA platform that detects microRNAs (miRNAs) by triggering ribosomal frameshifting. This molecular switch converts miRNA presence into a measurable protein output, enabling new diagnostic tools.
Area of Science:
- Molecular Biology
- Synthetic Biology
- Biotechnology
Background:
- Programmed -1 ribosomal frameshifting (-1 PRF) is a viral recoding mechanism.
- Frameshifting efficiency depends on mRNA secondary structure stability at frameshifting stimulating elements (FSEs).
Purpose of the Study:
- To develop a programmable mRNA-based platform for detecting specific microRNAs (miRNAs).
- To convert miRNA presence into a quantifiable protein output via miRNA-triggered -1 PRF.
Main Methods:
- Designed a triplex-forming mRNA (TF-mRNA) platform to trap target miRNAs.
- Utilized mRNA-miRNA-mRNA (miR-mRNA2) triplex formation to stimulate ribosomal frameshifting.
- Validated TF-mRNA binding affinity and dissociation rates using biolayer interferometry and fluorescence studies.
- Tested the system in a cell-free dual-luciferase translation system.
Main Results:
- TF-mRNA forms stable complexes with cognate miRNAs, exhibiting low nanomolar affinity and slow dissociation.
- miR-mRNA2 triplex formation robustly stimulated ribosomal frameshifting, acting as a miRNA-dependent switch.
- The TF-mRNA platform demonstrated generality for several disease-associated purine-rich miRNAs.
Conclusions:
- The programmable TF-mRNA platform effectively detects miRNAs by inducing -1 PRF.
- This platform serves as a foundation for novel diagnostic tools and synthetic biology circuits.
- The system translates miRNA detection into a quantifiable protein signal.
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