Reassigning stop codons via translation termination: How a few eukaryotes broke the dogma

BioEssays ◽  
2016 ◽  
Vol 39 (3) ◽  
pp. 1600213 ◽  
Author(s):  
Elena Alkalaeva ◽  
Tatiana Mikhailova
Keyword(s):  
Translation Termination ◽  
Stop Codons

Structural basis for ArfA–RF2-mediated translation termination on mRNAs lacking stop codons

Nature ◽  
2016 ◽  
Vol 541 (7638) ◽  
pp. 546-549 ◽  
Author(s):  
Paul Huter ◽  
Claudia Müller ◽  
Bertrand Beckert ◽  
Stefan Arenz ◽  
Otto Berninghausen ◽  
...  
Keyword(s):  
Translation Termination ◽  
Structural Basis ◽  
Stop Codons

Termination of translation in eukaryotes

1995 ◽  
Vol 73 (11-12) ◽  
pp. 1079-1086 ◽  
Author(s):  
Lev L. Kisselev ◽  
Lyudmila Yu. Frolova
Keyword(s):  
Polypeptide Chain ◽  
Translation Termination ◽  
Protein Biosynthesis ◽  
High Rate ◽  
Vitro Assay ◽  
Binding Motifs ◽  
Stop Codons ◽  
Release Factors ◽  
Terminal Domain ◽  
Gtp Binding

Termination of translation is governed in ribosomes by polypeptide chain release factors (pRF and eRF in prokaryotes and eukaryotes, respectively). In prokaryotes, three pRF have been identified and sequenced, while in eukaryotes, only a single eRF has been identified to date. Recently, we have characterized a highly conserved protein family called eRF1. At least, human and Xenopus laevis proteins from this family are active as eRFs in the in vitro assay with any of the three stop codons. No structural similarity has been revealed between any of the three pRFs and eRF1 family. Furthermore, GTP-binding motifs have not been revealed, although translation termination in eukaryotes is a GTP-dependent process. We have demonstrated that in eukaryotes a second eRF exists in addition to eRF1, called eRF3. The eRF3 family has two features in common: presence of GTP-binding motifs and high conservation of the C-terminal domain structure. The C-terminal domain of the X. laevis eRF3 has no RF activity although it stimulates the eRF1 activity considerably at low concentration of the stop codons, conferring GTP dependence to the termination reaction. Without eRF3, the eRF1 activity is entirely GTP independent. Some features of X. laevis eRF3 (C-terminal domain) resemble those of pRF3. The newly identified eRF1 and eRF3 are structurally conserved and distinct from the respective pRF1/2 and pRF3 proteins, pointing to the possibility of different evolution of translation termination machinery in prokaryotes and eukaryotes. Bipartition of the translation termination apparatus probably provides high rate and accuracy of translation termination.Key words: higher eukaryotic polypeptide chain release factors, translation termination, protein biosynthesis.

scholarly journals Distinct Paths To Stop Codon Reassignment by the Variant-Code Organisms Tetrahymena and Euplotes

2006 ◽  
Vol 26 (2) ◽  
pp. 438-447 ◽  
Author(s):  
Joe Salas-Marco ◽  
Hua Fan-Minogue ◽  
Adam K. Kallmeyer ◽  
Lawrence A. Klobutcher ◽  
Philip J. Farabaugh ◽  
...  
Keyword(s):  
Stop Codon ◽  
Translation Termination ◽  
Yeast Cells ◽  
Universal Genetic Code ◽  
Stop Codons ◽  
Codon Recognition ◽  
Ciliate Species ◽  
Stop Codon Recognition ◽  
Euplotes Octocarinatus

ABSTRACT The reassignment of stop codons is common among many ciliate species. For example, Tetrahymena species recognize only UGA as a stop codon, while Euplotes species recognize only UAA and UAG as stop codons. Recent studies have shown that domain 1 of the translation termination factor eRF1 mediates stop codon recognition. While it is commonly assumed that changes in domain 1 of ciliate eRF1s are responsible for altered stop codon recognition, this has never been demonstrated in vivo. To carry out such an analysis, we made hybrid proteins that contained eRF1 domain 1 from either Tetrahymena thermophila or Euplotes octocarinatus fused to eRF1 domains 2 and 3 from Saccharomyces cerevisiae. We found that the Tetrahymena hybrid eRF1 efficiently terminated at all three stop codons when expressed in yeast cells, indicating that domain 1 is not the sole determinant of stop codon recognition in Tetrahymena species. In contrast, the Euplotes hybrid facilitated efficient translation termination at UAA and UAG codons but not at the UGA codon. Together, these results indicate that while domain 1 facilitates stop codon recognition, other factors can influence this process. Our findings also indicate that these two ciliate species used distinct approaches to diverge from the universal genetic code.

scholarly journals Mutations in Eukaryotic Release Factors 1 and 3 Act as General Nonsense Suppressors in Drosophila

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 601-612
Author(s):  
Anna T Chao ◽  
Herman A Dierick ◽  
Tracie M Addy ◽  
Amy Bejsovec
Keyword(s):  
Stop Codon ◽  
Translation Termination ◽  
Nonsense Suppression ◽  
Release Factor ◽  
Nonsense Mutations ◽  
Stop Codons ◽  
Larval Stages ◽  
Mutant Phenotypes ◽  
Polypeptide Chains ◽  
Nonsense Suppressors

Abstract In a screen for suppressors of the Drosophila winglessPE4 nonsense allele, we isolated mutations in the two components that form eukaryotic release factor. eRF1 and eRF3 comprise the translation termination complex that recognizes stop codons and catalyzes the release of nascent polypeptide chains from ribosomes. Mutations disrupting the Drosophila eRF1 and eRF3 show a strong maternal-effect nonsense suppression due to readthrough of stop codons and are zygotically lethal during larval stages. We tested nonsense mutations in wg and in other embryonically acting genes and found that different stop codons can be suppressed but only a subset of nonsense alleles are subject to suppression. We suspect that the context of the stop codon is significant: nonsense alleles sensitive to suppression by eRF1 and eRF3 encode stop codons that are immediately followed by a cytidine. Such suppressible alleles appear to be intrinsically weak, with a low level of readthrough that is enhanced when translation termination is disrupted. Thus the eRF1 and eRF3 mutations provide a tool for identifying nonsense alleles that are leaky. Our findings have important implications for assigning null mutant phenotypes and for selecting appropriate alleles to use in suppressor screens.

scholarly journals Ribosome recycling factor ABCE1 depletion inhibits nonsense-mediated mRNA decay by promoting stop codon readthrough

2019 ◽  
Author(s):  
Giuditta Annibaldis ◽  
René Dreos ◽  
Michal Domanski ◽  
Sarah Carl ◽  
Oliver Mühlemann
Keyword(s):  
Mrna Decay ◽  
Stop Codon ◽  
Translation Termination ◽  
Ribosome Profiling ◽  
List Type ◽  
Ribosome Recycling Factor ◽  
Stop Codons ◽  
Nonsense Mediated Mrna Decay ◽  
Ribosome Disassembly ◽  
Stop Codon Readthrough

SUMMARYNonsense-mediated mRNA decay (NMD) is an essential post-transcriptional surveillance pathway in vertebrates that appears to be mechanistically linked with translation termination. To gain more insight into this connection, we interfered with translation termination by depleting human cells of the ribosome recycling factor ABCE1, which resulted in an upregulation of many but not all endogenous NMD-sensitive mRNAs. Notably, the suppression of NMD on these mRNAs occurs at a step prior to their SMG6-mediated endonucleolytic cleavage. Ribosome profiling revealed that ABCE1 depletion results in ribosome stalling at stop codons and increased ribosome occupancy in 3’ UTRs, indicative of enhanced stop codon readthrough or re-initiation. Using reporter genes, we further demonstrate that the absence of ABCE1 indeed increases the rate of readthrough, which would explain the observed NMD inhibition, since enhanced readthrough has been previously shown to render NMD-sensitive transcripts resistant to NMD by displacing NMD triggering factors like UPF1 and exon junction complexes (EJCs) from the 3’ UTR. Collectively, our results show that improper ribosome disassembly interferes with proper NMD activation.HighlightsABCE1 knockdown suppresses NMD of many NMD-sensitive mRNAsThe observed NMD inhibition occurs at a stage prior to SMG6-mediated cleavage of the mRNAABCE1 depletion enhances ribosome occupancy at stop codons and in the 3’ UTRABCE1 depletion enhances readthrough of the stop codonEnhanced readthrough inhibits NMD, presumably by clearing the 3’ UTR of NMD factors

Translation termination in human mitochondrial ribosomes

2010 ◽  
Vol 38 (6) ◽  
pp. 1523-1526 ◽  
Author(s):  
Ricarda Richter ◽  
Aleksandra Pajak ◽  
Sven Dennerlein ◽  
Agata Rozanska ◽  
Robert N. Lightowlers ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxidative Phosphorylation ◽  
Translation Termination ◽  
Open Reading Frame ◽  
Standard Genetic Code ◽  
Reading Frame ◽  
Stop Codons ◽  
Mitochondrial Ribosomes ◽  
Mammalian Mitochondria ◽  
Higher Eukaryotes

Mitochondria are ubiquitous and essential organelles for all nucleated cells of higher eukaryotes. They contain their own genome [mtDNA (mitochondrial DNA)], and this autosomally replicating extranuclear DNA encodes a complement of genes whose products are required to couple oxidative phosphorylation. Sequencing of this human mtDNA more than 20 years ago revealed unusual features that included a modified codon usage. Specific deviations from the standard genetic code include recoding of the conventional UGA stop to tryptophan, and, strikingly, the apparent recoding of two arginine triplets (AGA and AGG) to termination signals. This latter reassignment was made because of the absence of cognate mtDNA-encoded tRNAs, and a lack of tRNAs imported from the cytosol. Each of these codons only occurs once and, in both cases, at the very end of an open reading frame. The presence of both AGA and AGG is rarely found in other mammals, and the molecular mechanism that has driven the change from encoding arginine to dictating a translational stop has posed a challenging conundrum. Mitochondria from the majority of other organisms studied use only UAA and UAG, leaving the intriguing question of why human organelles appear to have added the complication of a further two stop codons, AGA and AGG, or have they? In the present review, we report recent data to show that mammalian mitochondria can utilize a −1 frameshift such that only the standard UAA and UAG stop codons are required to terminate the synthesis of all 13 polypeptides.

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