The Influence of A/G Composition of 3' Stop Codon Contexts on Translation Termination Efficiency in Eukaryotes
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CULAR CELL BIOLOGY UDC 577.217.562
The Influence of A/G Composition of 3' Stop Codon Contexts on Translation Termination Efficiency in Eukaryotes E. E. Sokolovaa, P. K. Vlasovb, T. V. Egorovaa, A. V. Shuvalova, and E. Z. Alkalaevaa, * a
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia bInstitute of Science and Technology, Klosterneuburg, 3400 Austria *e-mail: [email protected] Received February 27, 2020; revised March 20, 2020; accepted March 26, 2020
Abstract—Translation termination is a finishing step of protein biosynthesis. The significant role in this process belongs not only to protein factors of translation termination but also to the nearest nucleotide environment of stop codons. There are numerous descriptions of stop codons readthrough, which is due to specific nucleotide sequences behind them. However, represented data are segmental and don’t explain the mechanism of the nucleotide context influence on translation termination. It is well known that stop codon UAA usage is preferential for A/T-rich genes, and UAG, UGA—for G/C-rich genes, which is related to an expression level of these genes. We investigated the connection between a frequency of nucleotides occurrence in 3' area of stop codons in the human genome and their influence on translation termination efficiency. We found that 3' context motif, which is cognate to the sequence of a stop codon, stimulates translation termination. At the same time, the nucleotide composition of 3' sequence that differs from stop codon, decreases translation termination efficiency. Keywords: stop codon, 3' context, translation termination, stop codon readthrough, ribosome DOI: 10.1134/S0026893320050088
INTRODUCTION Termination of translation is realized by the release factors of class I and II (RF1/RF2 and RF3 in prokaryote cells; eRF1 and eRF3 in eukaryotes) [1, 2]. Class I factors recognize stop codons on mRNA at the A-site of a small ribosome subunit, and trigger hydrolysis of the peptidyl-tRNA ether bond at the peptidyl transferase center of a large ribosomal subunit. Class II factors are GTPases contributing factors of class I. Nucleotide sequences surrounding stop codons are known to influence translation termination and thus control protein synthesis. Analysis of mRNA regions around stop codons suggests that termination efficiency can be controlled not only by the stop codon but also, additionally, by the nucleotides surrounding it. The frequencies of stop codon usage vary significantly among different groups of organisms. UGA terminating codon is commonly used in mammals and monocotyledonous plants. UAA preferred in all other eukaryotes except Drosophila, in which the most frequent stop codon is UAG. At the same time, in all other groups of eukaryotes, UAG-codon refers to rare [3–6]. The prevalence of stop codons in prokaryotes and eukaryotes is the same: the most frequent terminating codon is UAA, and UGA is the rarest [7]. The bioinformatics analysis of frequencies of the nucleotides surrounding stop codons sho
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