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Selection of start codon during mRNA scanning in eukaryotic translation initiation

Basu, I and Gorai, B and Chandran, T and Maiti, PK and Hussain, T (2022) Selection of start codon during mRNA scanning in eukaryotic translation initiation. In: Communications Biology, 5 (1).

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Official URL: https://doi.org/10.1038/s42003-022-03534-2


Abstract Accurate and high-speed scanning and subsequent selection of the correct start codon are important events in protein synthesis. Eukaryotic mRNAs have long 5′ UTRs that are inspected for the presence of a start codon by the ribosomal 48S pre-initiation complex (PIC). However, the conformational state of the 48S PIC required for inspecting every codon is not clearly understood. Here, atomistic molecular dynamics (MD) simulations and energy calculations suggest that the scanning conformation of 48S PIC may reject all but 4 (GUG, CUG, UUG and ACG) of the 63 non-AUG codons, and initiation factor eIF1 is crucial for this discrimination. We provide insights into the possible role of initiation factors eIF1, eIF1A, eIF2α and eIF2β in scanning. Overall, the study highlights how the scanning conformation of ribosomal 48S PIC acts as a coarse selectivity checkpoint for start codon selection and scans long 5′ UTRs in eukaryotic mRNAs with accuracy and high speed.

Item Type: Journal Article
Publication: Communications Biology
Publisher: Nature Research
Additional Information: The copyright for this article belongs to the Authors.
Keywords: initiation factor 1; messenger RNA, 5' untranslated region; genetics; metabolism; start codon; translation initiation, 5' Untranslated Regions; Codon, Initiator; Eukaryotic Initiation Factor-1; Peptide Chain Initiation, Translational; RNA, Messenger
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 17 Sep 2022 03:17
Last Modified: 17 Sep 2022 03:17
URI: https://eprints.iisc.ac.in/id/eprint/76571

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