Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions

Chen, Jin; Coakley, Arthur; O’Connor, Michelle; Petrov, Alexey; O’Leary, Seán E.; Atkins, John F.; Puglisi, Joseph D.

doi:10.1016/j.cell.2015.10.064

Cited by 48 publications

(94 citation statements)

References 49 publications

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“…Nascent peptide-ribosome interactions often play an important role in regulation of translation (Ito and Chiba, 2013) and can influence certain recoding events (Chen et al, 2015; Gupta et al, 2013; Samatova et al, 2014; Weiss et al, 1990; Yordanova et al, 2015). We considered the possibility that the CopA nascent chain might affect the frequency of -1 PRF and hence play a role in controlling the relative expression of CopA(Z) and CopA proteins from the same gene.…”

Section: Resultsmentioning

confidence: 99%

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

et al. 2017

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Summary Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 amino acid-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations. The high efficiency of frameshifting is achieved by the combined stimulatory action of a ‘slippery’ sequence, an mRNA pseudoknot, and the CopA nascent chain. Similar mRNA elements are not only found in the copA genes of other bacteria but are also present in ATP7B, the human homolog of copA, and direct ribosomal frameshifting in vivo.

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Section: Resultsmentioning

confidence: 99%

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

et al. 2017

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“…The subsequent codon is a stop codon UAG, but instead of terminating protein synthesis, the ribosome slides over a 50 nt-long non-coding gap, lands at a distal GGA codon and resumes translation to the end of ORF2 (132). Gene 60 mRNA elements that stimulate bypassing are located 5 of the take-off site, in the take-off SL and 3 of the landing site (132)(133)(134)(135)(136). Remarkably, the key bypassing signals, such as the take-off SL element and the matching take-off and landing codons, are present also in yeast mitochondrial bypassing mRNAs (129), suggesting a similar mechanism of bypassing to that in bacteriophage T4.…”

Section: Translational Bypassingmentioning

confidence: 99%

“…Recent biochemical, single molecule and structural work suggests how translational bypassing works. Translation of ORF1 is a non-uniform process: at the beginning, translation of ORF1 is rapid but then gradually slows down (136), probably because the ribosome has to unwind the secondary structure elements on its way along the mRNA. The ribosome pauses at the take-off GGA codon (136).…”

Section: Translational Bypassingmentioning

confidence: 99%

“…Translation of ORF1 is a non-uniform process: at the beginning, translation of ORF1 is rapid but then gradually slows down (136), probably because the ribosome has to unwind the secondary structure elements on its way along the mRNA. The ribosome pauses at the take-off GGA codon (136). To start bypassing, the ribosome requires the action of EF-G accompanied with GTP hydrolysis and a rotation of the ribosomal subunits relative to each other into an unusual hyperrotated conformation (137).…”

Section: Translational Bypassingmentioning

confidence: 99%

“…This GTP expenditure may be required to maintain the ribosome conformation that is prone to sliding or to facilitate the forward direction of sliding, similarly to the power-stroke action of EF-G in translocation (138). Although all ribosomes disengage from the take-off GGA codon and start sliding, only 50-60% of them synthesize the full-length protein, while the remaining ribosomes stop translation due to termination or spontaneous dropoff of the peptidyl-tRNA Gly (135,136,139). At the end of the non-coding mRNA gap, the ribosome lands at the GGA codon guided by the 3 SL in the mRNA downstream of the landing codon (135).…”

Section: Translational Bypassingmentioning

confidence: 99%

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Translational recoding: canonical translation mechanisms reinterpreted

Rodnina

Korniy

Klimova

et al. 2019

Nucleic Acids Research

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During canonical translation, the ribosome moves along an mRNA from the start to the stop codon in exact steps of one codon at a time. The collinearity of the mRNA and the protein sequence is essential for the quality of the cellular proteome. Spontaneous errors in decoding or translocation are rare and result in a deficient protein. However, dedicated recoding signals in the mRNA can reprogram the ribosome to read the message in alternative ways. This review summarizes the recent advances in understanding the mechanisms of three types of recoding events: stop-codon readthrough, -1 ribosome frameshifting and translational bypassing. Recoding events provide insights into alternative modes of ribosome dynamics that are potentially applicable to other non-canonical modes of prokaryotic and eukaryotic translation.

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Dissipation and Control in Microscopic Nonequilibrium Systems

Large¹

2021

Springer Theses

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Quantifying the flow of energy, entropy, and information within and through nonequilibrium systems remains a central challenge in understanding the microscopic physics of biological systems. Over the past two and a half decades, parallel developments in the fields of theoretical stochastic thermodynamics and single-molecule experiments have made tremendous steps towards this end, advancing our understanding of the fundamental physical limitations and constraints faced by biological systems in vivo. Central in this focus are molecular machines: nanoscale protein complexes which interconvert between different forms of energy to perform useful functions to the cell. While single-molecule experiments on molecular machines have predicted impressively high efficiencies, much is still unknown about their performance in vivo. In this thesis we build upon these primitives, largely by making use of near-equilibrium phenomenological models to simplify and make tractable the problem of quantifying dissipation in molecular machines and predicting the operational modes which are imperative to minimizing their dissipation. By exploring the relevance of near-equilibrium models in the experimental investigation of a DNA hairpin, we find that such an approach can provide utility in understanding the strategies to reduce dissipation in nonequilibrium processes. However, single-molecule manipulations are significantly separated from the in vivo dynamics of molecular machines, and thus for the remainder of the thesis we expand upon this approach in various ways, generalizing the existing theoretical framework to more closely parallel the dynamics of molecular machines. By incorporating the inter-system feedback present in molecular machines, we find that familiar intuitions about how excess work and entropy production are related break down. Finally, we derive a phenomenological expression for the energy flows communicated within the components of a mechanochemical molecular machine. Ultimately, our analysis shows that intersystem feedback can lead to nonvanishing energy flows which are the manifestation of a Maxwell demon in the molecular machine itself.

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Coupling of mRNA Structure Rearrangement to Ribosome Movement during Bypassing of Non-coding Regions

Cited by 48 publications

References 49 publications

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

Translational recoding: canonical translation mechanisms reinterpreted

Dissipation and Control in Microscopic Nonequilibrium Systems

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