New universal rules of eukaryotic translation initiation fidelity.

The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5'end until an ATG codon with a specific nucleotide (nt) context surrounding it is recognized (Kozak rule). According to this model, ATG codons upstream to t...

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Autores principales:	Hadas Zur, Tamir Tuller
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1186f3de39074d56bdb8c40ddfa3a287
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spelling	oai:doaj.org-article:1186f3de39074d56bdb8c40ddfa3a2872021-11-18T05:52:01ZNew universal rules of eukaryotic translation initiation fidelity.1553-734X1553-735810.1371/journal.pcbi.1003136https://doaj.org/article/1186f3de39074d56bdb8c40ddfa3a2872013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874179/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5'end until an ATG codon with a specific nucleotide (nt) context surrounding it is recognized (Kozak rule). According to this model, ATG codons upstream to the beginning of the ORF should affect translation. We perform for the first time, a genome-wide statistical analysis, uncovering a new, more comprehensive and quantitative, set of initiation rules for improving the cost of translation and its efficiency. Analyzing dozens of eukaryotic genomes, we find that in all frames there is a universal trend of selection for low numbers of ATG codons; specifically, 16-27 codons upstream, but also 5-11 codons downstream of the START ATG, include less ATG codons than expected. We further suggest that there is selection for anti optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and fidelity of translation initiation is encoded in the 5'UTR as required by the scanning model, but also at the beginning of the ORF. The observed nt patterns suggest that in all the analyzed organisms the pre-initiation complex often misses the START ATG of the ORF, and may start translation from an alternative initiation start-site. Thus, to prevent the translation of undesired proteins, there is selection for nucleotide sequences with low affinity to the pre-initiation complex near the beginning of the ORF. With the new suggested rules we were able to obtain a twice higher correlation with ribosomal density and protein levels in comparison to the Kozak rule alone (e.g. for protein levels r=0.7 vs. r=0.31; p<10(-12)).Hadas ZurTamir TullerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 7, p e1003136 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Hadas Zur Tamir Tuller New universal rules of eukaryotic translation initiation fidelity.
description	The accepted model of eukaryotic translation initiation begins with the scanning of the transcript by the pre-initiation complex from the 5'end until an ATG codon with a specific nucleotide (nt) context surrounding it is recognized (Kozak rule). According to this model, ATG codons upstream to the beginning of the ORF should affect translation. We perform for the first time, a genome-wide statistical analysis, uncovering a new, more comprehensive and quantitative, set of initiation rules for improving the cost of translation and its efficiency. Analyzing dozens of eukaryotic genomes, we find that in all frames there is a universal trend of selection for low numbers of ATG codons; specifically, 16-27 codons upstream, but also 5-11 codons downstream of the START ATG, include less ATG codons than expected. We further suggest that there is selection for anti optimal ATG contexts in the vicinity of the START ATG. Thus, the efficiency and fidelity of translation initiation is encoded in the 5'UTR as required by the scanning model, but also at the beginning of the ORF. The observed nt patterns suggest that in all the analyzed organisms the pre-initiation complex often misses the START ATG of the ORF, and may start translation from an alternative initiation start-site. Thus, to prevent the translation of undesired proteins, there is selection for nucleotide sequences with low affinity to the pre-initiation complex near the beginning of the ORF. With the new suggested rules we were able to obtain a twice higher correlation with ribosomal density and protein levels in comparison to the Kozak rule alone (e.g. for protein levels r=0.7 vs. r=0.31; p<10(-12)).
format	article
author	Hadas Zur Tamir Tuller
author_facet	Hadas Zur Tamir Tuller
author_sort	Hadas Zur
title	New universal rules of eukaryotic translation initiation fidelity.
title_short	New universal rules of eukaryotic translation initiation fidelity.
title_full	New universal rules of eukaryotic translation initiation fidelity.
title_fullStr	New universal rules of eukaryotic translation initiation fidelity.
title_full_unstemmed	New universal rules of eukaryotic translation initiation fidelity.
title_sort	new universal rules of eukaryotic translation initiation fidelity.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1186f3de39074d56bdb8c40ddfa3a287
work_keys_str_mv	AT hadaszur newuniversalrulesofeukaryotictranslationinitiationfidelity AT tamirtuller newuniversalrulesofeukaryotictranslationinitiationfidelity
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New universal rules of eukaryotic translation initiation fidelity.

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