Translation initiation factor elF3 promotes programmed stop codon readthrough

0452640 - MBÚ 2016 RIV GB eng J - Journal Article
Beznosková, Petra - Wagner, Susan - Jansen, Myrte Esmeralda - von der Haar, T. - Valášek, Leoš
Translation initiation factor elF3 promotes programmed stop codon readthrough.
Nucleic Acids Research. Roč. 43, č. 10 (2015), s. 5099-5111. ISSN 0305-1048. E-ISSN 1362-4962
R&D Projects: GA ČR(CZ) GA14-05394S
Institutional support: RVO:61388971
Keywords : EUKARYOTIC RELEASE FACTOR-1 * RNA RECOGNITION MOTIF * TICK FEVER VIRUS
Subject RIV: CE - Biochemistry
Impact factor: 9.202, year: 2015

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.
Permanent Link: http://hdl.handle.net/11104/0253587