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RNA Structural Ensemble Determinants of -1 Programmed Ribosomal Frameshifting Efficiency Across Coronavirus Evolution
Scott R Allen1, Tamar Schlick2, Alain Laederach1
1Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Journal of Molecular Biology
|October 30, 2025
Summary
This study reveals that the structural dynamics of coronavirus programmed ribosomal frameshifting (-1 PRF) elements are complex and not always linked to efficiency. Novel frameshifting elements (FSEs) show varied structures, challenging previous SARS-CoV-2 models.
Area of Science:
- Molecular Biology
- Virology
- Structural Biology
Background:
- Programmed ribosomal frameshifting (-1 PRF) is crucial for viral protein synthesis.
- Coronavirus -1 PRF elements exhibit complex structural ensembles essential for frameshifting efficiency.
- Previous studies on SARS-CoV-2 suggest structure-function relationships governing -1 PRF efficiency.
Purpose of the Study:
- To experimentally determine and characterize the structural ensembles of four novel -1 PRF elements.
- To correlate structural information with -1 PRF efficiency measurements.
- To investigate the structure-function relationships of frameshifting elements (FSEs) beyond SARS-CoV-2.
Main Methods:
- Experimental determination and characterization of structural ensembles for novel -1 PRF elements.
- Measurement of -1 PRF efficiency for these elements.
- Modular swapping of viral sequence elements to assess their impact on frameshifting.
Main Results:
- Structure-function relationships in SARS-CoV-2 do not fully generalize to other FSEs.
- Increased conformational diversity does not always correlate with higher -1 PRF efficiency; one efficient element adopted a single conformation.
- No single structural feature, including attenuator hairpin strength, predicts frameshifting efficiency; upstream sequence elements significantly modulate frameshifting.
Conclusions:
- Frameshifting efficiency is influenced by complex structural dynamics and sequence elements, not solely by conformational number or hairpin strength.
- The study highlights a trend away from canonical stem I formation in efficient FSEs.
- Characterized frameshifting elements may have biotechnological applications in gene therapy and protein expression control.
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