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真核生物中 AUG 起始密码子上下文的保守性和变异性。

Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes.

机构信息

Translation and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (Instituto Nacional de Cancerología, INCan), 22 San Fernando Avenue, Tlalpan, 14080 Mexico City, Mexico.

Translation and Cancer Laboratory, Unit of Biomedical Research on Cancer, National Institute of Cancer (Instituto Nacional de Cancerología, INCan), 22 San Fernando Avenue, Tlalpan, 14080 Mexico City, Mexico.

出版信息

Trends Biochem Sci. 2019 Dec;44(12):1009-1021. doi: 10.1016/j.tibs.2019.07.001. Epub 2019 Jul 25.


DOI:10.1016/j.tibs.2019.07.001
PMID:31353284
Abstract

Selection of the translation initiation site (TIS) is a crucial step during translation. In the 1980s Marylin Kozak performed key studies on vertebrate mRNAs to characterize the optimal TIS consensus sequence, the Kozak motif. Within this motif, conservation of nucleotides in crucial positions, namely a purine at -3 and a G at +4 (where the A of the AUG is numbered +1), is essential for TIS recognition. Ever since its characterization the Kozak motif has been regarded as the optimal sequence to initiate translation in all eukaryotes. We revisit here published in silico data on TIS consensus sequences, as well as experimental studies from diverse eukaryotic lineages, and propose that, while the -3A/G position is universally conserved, the remaining variability of the consensus sequences enables their classification as optimal, strong, and moderate TIS sequences.

摘要

翻译起始位点(TIS)的选择是翻译过程中的关键步骤。20 世纪 80 年代,Marylin Kozak 对脊椎动物 mRNA 进行了关键性研究,以确定最优的 TIS 共识序列,即 Kozak 基序。在这个基序中,关键位置的核苷酸(即在-3 位的嘌呤和+4 位的 G(AUG 的 A 编号为+1))的保守性对于 TIS 的识别至关重要。自从其特征被确定以来,Kozak 基序一直被认为是所有真核生物中启动翻译的最佳序列。我们重新审视了已发表的 TIS 共识序列的计算机数据,以及来自不同真核生物谱系的实验研究,并提出,虽然-3A/G 位置是普遍保守的,但共识序列的其余变异性使其能够被分类为最优、强和中等 TIS 序列。

相似文献

[1]
Conservation and Variability of the AUG Initiation Codon Context in Eukaryotes.

Trends Biochem Sci. 2019-7-25

[2]
Functional analysis of the AUG initiator codon context reveals novel conserved sequences that disfavor mRNA translation in eukaryotes.

Nucleic Acids Res. 2024-2-9

[3]
Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

Nucleic Acids Res. 2018-1-25

[4]
Translation initiation downstream from annotated start codons in human mRNAs coevolves with the Kozak context.

Genome Res. 2020-7

[5]
Prediction of translation initiation sites in human mRNA sequences with AUG start codon in weak Kozak context: A neural network approach.

Biochem Biophys Res Commun. 2008-5-16

[6]
Quantitative analysis of mammalian translation initiation sites by FACS-seq.

Mol Syst Biol. 2014-8-28

[7]
Computational approach for calculating the probability of eukaryotic translation initiation from ribo-seq data that takes into account leaky scanning.

BMC Bioinformatics. 2014-11-21

[8]
Identification of compounds that decrease the fidelity of start codon recognition by the eukaryotic translational machinery.

RNA. 2011-1-10

[9]
Quantification analysis of translation initiation signal in vertebrate mRNAs: effect of nucleotides at positions +4(-)+6 upon efficiency of translation initiation.

Nucleic Acids Symp Ser. 2000

[10]
AUG codons at the beginning of protein coding sequences are frequent in eukaryotic mRNAs with a suboptimal start codon context.

Bioinformatics. 2005-4-1

引用本文的文献

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NetStart 2.0: prediction of eukaryotic translation initiation sites using a protein language model.

BMC Bioinformatics. 2025-8-19

[2]
Patchy Phylogenetic Distribution and Poor Translational Adaptation of a Nested ORF in the Mammalian Mitochondrial Gene.

Genes (Basel). 2025-7-17

[3]
Ribosomal protein S25 promotes cell cycle entry for a productive BK polyomavirus infection.

Philos Trans R Soc Lond B Biol Sci. 2025-3-6

[4]
Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.

Proc Natl Acad Sci U S A. 2025-3-4

[5]
Multiplexed assays of human disease-relevant mutations reveal UTR dinucleotide composition as a major determinant of RNA stability.

Elife. 2025-2-18

[6]
AUGcontext DB: a comprehensive catalog of the mRNA AUG initiator codon context across eukaryotes.

RNA Biol. 2025-12

[7]
Deciphering Transcription in : Polycistronic Gene Expression and Chromatin Accessibility.

bioRxiv. 2025-1-18

[8]
The regulatory landscape of 5' UTRs in translational control during zebrafish embryogenesis.

Dev Cell. 2025-5-19

[9]
Kv3.3 Expression Enhanced by a Novel Variant in the Kozak Sequence of .

Int J Mol Sci. 2024-11-20

[10]
HOT3/eIF5B1 confers Kozak motif-dependent translational control of photosynthesis-associated nuclear genes for chloroplast biogenesis.

Nat Commun. 2024-11-14

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