Unraveling the landscapes and regulation of scanning, leaky scanning, and 48S initiation complex conformations.

Cell Rep

Department of Biomolecular Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address:

Published: May 2024

AI Article Synopsis

  • - The study focuses on translation initiation and scanning processes, examining how the proteins eIF4G1 and eIF1 affect the formation of the translation initiation complex (48S).
  • - The researchers used a technique called TCP-seq to analyze the organization of 48S and discovered that AUG context plays a significant role in determining the efficiency of translation initiation, especially in non-leaky genes.
  • - Their findings reveal distinct classes of initiation complexes, with one class being crucial for early initiation and another indicating a potential late initiation process, highlighting the dynamic nature of protein interactions during translation.

Article Abstract

Scanning and initiation are critical steps in translation. Here, we utilized translation complex profiling (TCP-seq) to investigate 48S organization and eIF4G1-eIF1 inhibition impact. We provide global views of scanning and leaky scanning, uncovering a central role of eIF4G1-eIF1 in their regulation. We confirm AUG context importance, with non-leaky genes featuring a Kozak context and cytosine at positions -1 and +5. Capturing 48S complexes associated with eIF1, eIF4G1, eIF3, and eIF2 through selective TCP-seq revealed that the eIF3-scanning ribosome is highly vulnerable to eIF4G1-eIF1 inhibition, and eIF1 tends to dissociate upon AUG recognition. Initiation-site footprint analysis revealed a class spanning -12 to +18/19 from the AUG, representing the entire 48S and enriched with eIF2, eIF1, and eIF4G1, indicative of early initiation. Another eIF3-dependent class extends up to +26 and exhibits reduced eIF2 and eIF4G1 association, suggesting a late/alternative initiation complex. Our analysis provides an overview of scanning, initiation, and evidence for conformational rearrangements in vivo.

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Source
http://dx.doi.org/10.1016/j.celrep.2024.114126DOI Listing

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