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  4. Single-mRNA imaging and modeling reveal coupled translation initiation and elongation rates
 
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Single-mRNA imaging and modeling reveal coupled translation initiation and elongation rates

Lamberti, Irene  
•
Chao, Jeffrey A
•
Gobet, Cédric  
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August 6, 2025

Abstract mRNA translation involves multiple regulatory steps, but how translation elongation in-fluences protein output remains unclear. Using SunTag live-cell imaging and mathematical modeling, we quantified translation dynamics in single mRNAs across diverse coding sequences. Our Totally Asymmetric Exclusion Process (TASEP)-based model revealed a strong coordination between initiation and elongation rates, resulting in consistently low ribosome density (≤12% occupancy) across all reporters. This coupling persisted under pharmacological inhibition of the elongation factor eIF5A, where proportional decreases in both initiation and elongation rates maintained homeostatic ribosome density. In contrast, eIF5A knockout cells exhibited a significant decrease in ribosome density, suggesting altered coordination. Together, these results highlight a dynamical coupling of initiation and elongation rates at the single-mRNA level, preventing ribosome crowding and maintaining translational homeostasis in mammalian cells.

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Type
preprint
DOI
10.7554/elife.107160
Author(s)
Lamberti, Irene  

École Polytechnique Fédérale de Lausanne

Chao, Jeffrey A
Gobet, Cédric  

École Polytechnique Fédérale de Lausanne

Naef, Felix  

École Polytechnique Fédérale de Lausanne

Date Issued

2025-08-06

Publisher

eLife Sciences Publications, Ltd

Written at

EPFL

EPFL units
UPNAE  
Available on Infoscience
August 21, 2025
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/253332
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