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Updated: Jan 12, 2026

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RNA Structural Ensemble Determinants of -1 Programmed Ribosomal Frameshifting Efficiency Across Coronavirus

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 summary is machine-generated.

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.

Keywords:

frameshifting element single molecule correlated chemical probing −1 programmed ribosomal frameshifting

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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.