Translation initiation factor eIF3 promotes programmed stop codon readthrough.

Beznoskova, Petra and Wagner, Susan and Jansen, Myrte E and von der Haar, Tobias and Valasek, Leos S (2015) Translation initiation factor eIF3 promotes programmed stop codon readthrough. Nucleic Acids Research, 43 (10). pp. 5099-5111. ISSN 0305-1048. (doi:https://doi.org/10.1093/nar/gkv421) (Full text available)

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Abstract

Programmed stop codon readthrough is a post-transcription regulatory mechanism specifically increasing proteome diversity by creating a pool of C-terminally extended proteins. During this process, the stop codon is decoded as a sense codon by a near-cognate tRNA, which programs the ribosome to continue elongation. The efficiency of competition for the stop codon between release factors (eRFs) and near-cognate tRNAs is largely dependent on its nucleotide context; however, the molecular mechanism underlying this process is unknown. Here, we show that it is the translation initiation (not termination) factor, namely eIF3, which critically promotes programmed readthrough on all three stop codons. In order to do so, eIF3 must associate with pre-termination complexes where it interferes with the eRF1 decoding of the third/wobble position of the stop codon set in the unfavorable termination context, thus allowing incorporation of near-cognate tRNAs with a mismatch at the same position. We clearly demonstrate that efficient readthrough is enabled by near-cognate tRNAs with a mismatch only at the third/wobble position. Importantly, the eIF3 role in programmed readthrough is conserved between yeast and humans.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QR Microbiology
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Tobias von der Haar
Date Deposited: 29 May 2015 12:12 UTC
Last Modified: 03 Jun 2015 14:31 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/48688 (The current URI for this page, for reference purposes)
von der Haar, Tobias: https://orcid.org/0000-0002-6031-9254
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