Single-chain models illustrate the 3D RNA folding shape during translation

Area of Science:

• Molecular Biology
• Biophysics
• Computational Biology

Background:

• The three-dimensional (3D) conformation of RNA is critical for its function and cellular fate.
• While mRNA is often modeled as a closed-loop structure, recent evidence suggests a single-chain polymer model may be more appropriate for many mRNAs.
• Understanding mRNA's 3D structure is essential for deciphering its localization, translation, and aggregation mechanisms.

Purpose of the Study:

• To introduce a novel computational tool, the Three-dimensional RNA Illustration Program (TRIP).
• To model the 3D folding shape of mRNA based on single-chain polymer principles.
• To investigate the relative contributions of base pairing versus polymer characteristics to mRNA's 3D conformation.

Main Methods:

• Developed the Three-dimensional RNA Illustration Program (TRIP) for simulating RNA folding.
• Utilized single-chain polymer models with angle restrictions for each component.
• Incorporated experimental data from single-molecule fluorescence in situ hybridization (smFISH) to validate simulations.

Main Results:

• TRIP successfully recapitulated mRNA conformational changes during translation.
• Simulations demonstrated the 3D positional interactions between organelles and localized mRNAs.
• Base-pairing interactions had minimal impact on 3D mRNA conformation; single-chain polymer properties were dominant.

Conclusions:

• mRNA's 3D conformation is primarily dictated by its single-chain polymer characteristics, not solely base pairing.
• The TRIP program provides a valuable tool for studying mRNA folding and dynamics.
• This top-down modeling approach can elucidate mRNA aggregation mechanisms in various cellular compartments.