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Reviews of "Single-Molecule Dynamics of SARS-CoV-2 5ʹ Cap Recognition by Human eIF4F"

Reviewers: 📗📗📗📗◻️ • Dixie Goss (CUNY) | 📒📒📒◻️◻️

Published onJul 21, 2021
Reviews of "Single-Molecule Dynamics of SARS-CoV-2 5ʹ Cap Recognition by Human eIF4F"
key-enterThis Pub is a Review of
Single-Molecule Dynamics of SARS-CoV-2 5’ Cap Recognition by Human eIF4F

ABSTRACTCoronaviruses initiate translation through recognition of the viral RNA 5’ m7GpppAm cap by translation factor eIF4F. eIF4F is a heterotrimeric protein complex with cap-binding, RNA-binding, and RNA helicase activities. Modulating eIF4F function through cellular regulation or small-molecule inhibition impacts coronavirus replication, including for SARS-CoV-2. Translation initiation involves highly coordinated dynamics of translation factors with messenger or viral RNA. However, how the eIF4F subunits coordinate on the initiation timescale to define cap-binding efficiency remains incompletely understood. Here we report that translation supported by the SARS-CoV-2 5’-UTR is highly sensitive to eIF4A inhibition by rocaglamide. Through a single-molecule fluorescence approach that reports on eIF4E–cap interaction, we dissect how eIF4F subunits contribute to cap-recognition efficiency on the SARS-CoV-2 5’ UTR. We find that free eIF4A enhances cap accessibility for eIF4E binding, but eIF4G alone does not change the kinetics of eIF4E–RNA interaction. Conversely, formation of the full eIF4F complex significantly alters eIF4E–cap interaction, suggesting that coordinated eIF4E and eIF4A activities establish the net eIF4F–cap recognition efficiency. Moreover, the eIF4F complex formed with phosphomimetic eIF4E(S209D) binds the viral UTR more efficiently than with wild-type eIF4E. These results highlight a dynamic interplay of eIF4F subunits and mRNA that determines cap-recognition efficiency.

To read the original manuscript, click the link above.

Summary of Reviews: This preprint uses a single molecular assay to demonstrate that SARS-CoV-2 5’ translation is sensitive to the small molecule rocaglamide. Reviewers deem the methodology reliable with only minor follow-up experiments.

Reviewer 1 | 📗📗📗📗◻️

Reviewer 2 (Dixie Goss) | 📒📒📒 ◻️◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below. 

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