Spontaneous Ribosome Bypassing in Growing Cells

Lindsley, Dale; Gallant, Jonathan; Doneanu, Catalin E.; Bonthuis, Paul J.; Caldwell, Seth D.; Fontelera, Ashley

doi:10.1016/j.jmb.2005.03.031

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…In some clade 5 sequences, the A-site codon is the ‘hungry’ sense codon AGG, which constitutes only 0.08% of codons in Acinetobacter, the natural host of these phages. This indicates that the cognate tRNA is similarly rare and predicts relevance of very slow decoding, consistent with results from frameshifting [25, 49], non-programmed bypassing [50] and yeast mitochondrial byp bypassing [13].…”

Section: Discussionsupporting

confidence: 82%

An RNA sequence that reprograms ribosomes to bypass a 50 nucleotide coding gap is encoded by a mobile element whose sequence conservation illuminates its bypass mechanisms

Manning

Atkins

2022

Preprint

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Background: A remarkable sequence in phage T4 causes ribosomes to skip over a 50 nucleotide insert within a topoisomerase subunit gene, and resume correct synthesis of the protein at a high efficiency. Its mechanism has been extensively studied but it remained an isolated phenomenon whose origin and full function are still a mystery. Results: We have found dozens of homologous cases in genomic and metagenomic sequences, all part of a mobile DNA element that repeatedly inserts in topoisomerase genes of Myoviridae phages. These have substantial sequence diversity, with selective conservation that specify the elaborate set of mechanisms found experimentally to underlie this extreme case of translational recoding. These sequences provide new variations on these mechanisms, and introduce additional features that may also be important for bypassing. These include a series of RNA secondary structures, a conserved stop codon or rare 'hungry' codon at the start of the bypass, a Shine-Dalgarno sequence flanked by AU-rich sequence, and residues in the nascent peptide that prime the ribosome for bypassing. Conclusions: These data provide an evolutionary foundation for the experimentally derived mechanisms, highlight several new features of the sequence, and provide substantial new variations on the bypass theme that will allow further experimental exploration of biologically meaningful variants.

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Section: Discussionsupporting

confidence: 82%

An RNA sequence that reprograms ribosomes to bypass a 50 nucleotide coding gap is encoded by a mobile element whose sequence conservation illuminates its bypass mechanisms

Manning

Atkins

2022

Preprint

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“…In the mechanism proposed here, bypassing is not induced by A-site (UAG stop codon) starvation, explaining why the absence of RF1 did not significantly affect the bypassing efficiency (Herr et al, 2000b). Bypassing induced by A-site starvation may follow a different mechanism (Lindsley et al, 2005a; Lindsley et al, 2005b). …”

Section: Discussionmentioning

confidence: 99%

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

Chen

Coakley

O’Connor

et al. 2015

Cell

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SUMMARY Nearly half of the ribosomes translating a particular bacteriophage T4 mRNA bypass 50 nucleotides in its middle, resuming translation 3’ of this region. How this large-scale, specific hop occurs, and what determines whether a ribosome bypasses, remains unclear. We apply single-molecule fluorescence with zero-mode waveguides to track individual Escherichia coli ribosomes during translation of T4's gene 60 mRNA. Ribosomes that bypass are characterized by a 10- to 20-fold longer pause in a non-canonical rotated state at the take-off codon. During the pause, mRNA secondary structure rearrangements are coupled to ribosome forward movement, facilitated by nascent peptide interactions that disengage the ribosome anticodon-codon interactions for slippage. Close to the landing site, the ribosome then scans the mRNA in search of the optimal base-pairing interactions. Our results provide a mechanistic and conformational framework for bypassing, highlighting a non-canonical ribosomal state to allow for mRNA structure refolding to drive large-scale ribosome movements.

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“…Since not only limitation of Ile-tRNA causes bypass, the ability to bypass upon limitation of an amino acid seems general, provided that reasonable takeoff and landing sites are available in the mRNA sequence. However, this kind of bypassing also occurs in logarithmically growing cells without imposing any aminoacyl-tRNA limitation (190). In the studies described above, the values directly measured reflect the combination of anticodon dissociation and repairing to mRNA, whereas in a complementary study the values reflect only re-pairing (51).…”

Section: Synthetic Perturbationsmentioning

confidence: 99%

A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment

Atkins

Björk

2009

Microbiol Mol Biol Rev

128

126

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SUMMARYMutants of translation components which compensate for both −1 and +1 frameshift mutations showed the first evidence for framing malleability. Those compensatory mutants isolated in bacteria and yeast with altered tRNA or protein factors are reviewed here and are considered to primarily cause altered P-site realignment and not altered translocation. Though the first sequenced tRNA mutant which suppressed a +1 frameshift mutation had an extra base in its anticodon loop and led to a textbook “yardstick” model in which the number of anticodon bases determines codon size, this model has long been discounted, although not by all. Accordingly, the reviewed data suggest that reading frame maintenance and translocation are two distinct features of the ribosome. None of the −1 tRNA suppressors have anticodon loops with fewer than the standard seven nucleotides. Many of the tRNA mutants potentially affect tRNA bending and/or stability and can be used for functional assays, and one has the conserved C74 of the 3′ CCA substituted. The effect of tRNA modification deficiencies on framing has been particularly informative. The properties of some mutants suggest the use of alternative tRNA anticodon loop stack conformations by individual tRNAs in one translation cycle. The mutant proteins range from defective release factors with delayed decoding of A-site stop codons facilitating P-site frameshifting to altered EF-Tu/EF1α to mutant ribosomal large- and small-subunit proteins L9 and S9. Their study is revealing how mRNA slippage is restrained except where it is programmed to occur and be utilized.

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Spontaneous Ribosome Bypassing in Growing Cells

Cited by 11 publications

References 23 publications

An RNA sequence that reprograms ribosomes to bypass a 50 nucleotide coding gap is encoded by a mobile element whose sequence conservation illuminates its bypass mechanisms

An RNA sequence that reprograms ribosomes to bypass a 50 nucleotide coding gap is encoded by a mobile element whose sequence conservation illuminates its bypass mechanisms

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

A Gripping Tale of Ribosomal Frameshifting: Extragenic Suppressors of Frameshift Mutations Spotlight P-Site Realignment

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