The Molecular Mechanics of Eukaryotic Translation

Kapp, Lee D.; Lorsch, Jon R.

doi:10.1146/annurev.biochem.73.030403.080419

Cited by 478 publications

(465 citation statements)

References 324 publications

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“…The process of translation initiation occurs by a series of key steps (for review, see Kapp and Lorsch 2004). For cap-dependent translation, which is the major mode of translation initiation, the 5Ј m7GpppG cap is recognized by the cap-binding protein, eIF-4E, part of the eIF-4F initiation complex.…”

Section: Translation Initiation Control Mechanisms and Their Implicatmentioning

confidence: 99%

Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.

Valencia-Sanchez¹,

Liu²,

Hannon³

et al. 2006

Genes Dev.

1,867

1,355

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The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro RNAs (miRNAs) and short interfering RNAs (siRNAs) and can affect mRNA degradation and translation, as well as chromatin structure, thereby having impacts on transcription rates. In this review, we discuss possible mechanisms by which miRNAs control translation and mRNA degradation. An emerging theme is that miRNAs, and siRNAs to some extent, target mRNAs to the general eukaryotic machinery for mRNA degradation and translation control.

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Section: Translation Initiation Control Mechanisms and Their Implicatmentioning

confidence: 99%

Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.

Valencia-Sanchez¹,

Liu²,

Hannon³

et al. 2006

Genes Dev.

1,867

1,355

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show abstract

“…During the incorporation of each successive amino acid, there are several stages at which the identity of the codon being translated may potentially influence the speed with which a ribosome advances along a coding sequence. When a codon is presented in the A-site of a ribosome, an appropriate tRNA must diffuse into the A-site and successfully form a codon-anticodon base pairing interaction [2,3]. tRNAs decoding different codons are expressed at different abundances [4,5], suggesting that ribosomes could spend longer waiting for less abundant tRNAs to arrive [6].…”

Section: Introductionmentioning

confidence: 99%

Understanding biases in ribosome profiling experiments reveals signatures of translation dynamics in yeast

Hussmann

Patchett

Johnson

et al. 2015

Preprint

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Ribosome profiling produces snapshots of the locations of actively translating ribosomes on messenger RNAs. These snapshots can be used to make inferences about translation dynamics. Recent ribosome profiling studies in yeast, however, have reached contradictory conclusions regarding the average translation rate of each codon. Some experiments have used cycloheximide (CHX) to stabilize ribosomes before measuring their positions, and these studies all counterintuitively report a weak negative correlation between the translation rate of a codon and the abundance of its cognate tRNA. In contrast, some experiments performed without CHX report strong positive correlations. To explain this contradiction, we identify unexpected patterns in ribosome density downstream of each type of codon in experiments that use CHX. These patterns are evidence that elongation continues to occur in the presence of CHX but with dramatically altered codon-specific elongation rates. The measured positions of ribosomes in these experiments therefore do not reflect the amounts of time ribosomes spend at each position in vivo. These results suggest that conclusions from experiments in yeast using CHX may need reexamination. In particular, we show that in all such experiments, codons decoded by less abundant tRNAs were in fact being translated more slowly before the addition of CHX disrupted these dynamics. Author SummaryRibosome profiling measures the precise locations of millions of actively translating ribosomes on mRNAs. In theory, the frequency with which ribosomes are observed positioned over each type of codon can be used to quantify the speed with which each codon is translated. In practice, ribosome profiling experiments in yeast that use translation inhibitors to arrest translation before measuring the positions of ribosomes report very different Data Availability Statement: Sequencing data has been deposited to the SRA with accession number SRP060588.Funding: This work was supported by NIH grant R01-GM-093086 to SS and NIH grant GM053655 to AJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing Interests: The authors have declared that no competing interests exist.apparent translation speeds for each codon than experiments that do not use inhibitors.To explain this inconsistency, we show that a previously unappreciated mechanism causes experiments using translation inhibitors to not measure ribosomes at each position on mRNAs in proportion to the actual amount of time spent there in vivo. Understanding this mechanism reveals that experiments without inhibitors more accurately measure translation dynamics and provides guidance for the design and interpretation of future ribosome profiling experiments.

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“…Instead, it is eIF5B that is the eukaryotic orthologue of bacterial IF2. eIF5B does not directly bind tRNA but, just as proposed for bacterial IF2, facilitates association of the two ribosomal subunits (4).…”

mentioning

confidence: 97%

Mitochondrial Initiation Factor 2 of Trypanosoma brucei Binds Imported Formylated Elongator-type tRNAMet

Charrière

Tan

Schneider

2005

Journal of Biological Chemistry

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The mitochondrion of Trypanosoma brucei lacks tRNA genes. Its translation system therefore depends on the import of nucleus-encoded tRNAs. Thus, except for the cytosol-specific initiator tRNA Met , all trypanosomal tRNAs function in both the cytosol and the mitochondrion. The only tRNA Met present in T. brucei mitochondria is therefore the one which, in the cytosol, is involved in translation elongation. Mitochondrial translation initiation depends on an initiator tRNA Met carrying a formylated methionine. This tRNA is then recognized by initiation factor 2, which brings it to the ribosome. To guarantee mitochondrial translation initiation, T. brucei has an unusual methionyl-tRNA formyltransferase that formylates elongator tRNA Met . In the present study, we have identified initiation factor 2 of T. brucei and shown that its carboxyl-terminal domain specifically binds formylated trypanosomal elongator tRNA Met . Furthermore, the protein also recognizes the structurally very different Escherichia coli initiator tRNA Met , suggesting that the main determinant recognized is the formylated methionine. In vivo studies using stable RNA interference cell lines showed that knockdown of initiation factor 2, depending on which construct was used, causes slow growth or even growth arrest. Moreover, concomitantly with ablation of the protein, a loss of oxidative phosphorylation was observed. Finally, although ablation of the methionyltRNA formyltransferase on its own did not impair growth, a complete growth arrest was observed when it was combined with the initiation factor 2 RNA interference cell line showing the slow growth phenotype. Thus, these experiments illustrate the importance of mitochondrial translation initiation for growth of procyclic T. brucei.

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The Molecular Mechanics of Eukaryotic Translation

Cited by 478 publications

References 324 publications

Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.

Control of translation and mRNA degradation by miRNAs and siRNAs: Table 1.

Understanding biases in ribosome profiling experiments reveals signatures of translation dynamics in yeast

Mitochondrial Initiation Factor 2 of Trypanosoma brucei Binds Imported Formylated Elongator-type tRNAMet

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