Restoration of In-phase Translation by an Unlinked Suppressor of a Frameshift Mutation in Salmonella typhimurium

Yourno, Joseph; Tanemura, Shigegi

doi:10.1038/225422a0

Cited by 56 publications

(32 citation statements)

References 17 publications

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“…In the case of frameshift mutations, it might be suggested that normal, nonmutated tRNAs could read 2-or 4-letter codons at a low frequency. Such a mechanism is known to be used by specific frameshift suppressors that appear to be mutated or modified tRNAs (3)(4)(5)(6).…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, frameshift mutants of bacteria have been studied to find out how fixed the present genetic code is in always having three as the reading unit. Frameshift mutations can be externally suppressed (3)(4)(5) by the reading of a non-triplet codon (4). Recent studies (6) have demonstrated that one class of external suppressors is altered in the structural gene for a minor tRNA species, and another class is defective in the enzymic modification of a minor tRNA species.…”

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confidence: 99%

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Low Activity of β-Galactosidase in Frameshift Mutants of Escherichia coli

Atkins

Elseviers

Gorini

1972

Proc. Natl. Acad. Sci. U.S.A.

107

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ABSTRACT16 lac frameshift mutants induced by an acridine derivative, ICR-191D, in E. coli are leaky for fl-galactosidase activity. Activities of all mutants differ from each other and from the wild type in their stability to thermal denaturation. The leakiness is under ribosomal control, since it is strongly reduced by strA restrictive mutations and is restored by ram mutations that reverse restriction. Addition of streptomycin during growth has an effect similar to the presence of the ram mutation. These ribosomal alterations do not modify the thermal stability of the enzyme.It is suggested that the leakiness is due to an infrequent 2-or 4-base reading close to the frameshift mutation site. The possibility that not only the ribosome, but also the reading context in the messenger, plays a role in securing code fidelity is discussed.Studies with frameshift mutations in phage T4 revealed the triplet nature of the genetic code (1, 2). Subsequently, frameshift mutants of bacteria have been studied to find out how fixed the present genetic code is in always having three as the reading unit. Frameshift mutations can be externally suppressed (3-5) by the reading of a non-triplet codon (4). Recent studies (6) have demonstrated that one class of external suppressors is altered in the structural gene for a minor tRNA species, and another class is defective in the enzymic modification of a minor tRNA species.It was originally assumed to be obvious that frameshift mutants should be completely negative unless the mutation occurs toward the end of the peptide chain, where an altered aminoacid sequence might not completely damage protein activity. In one case, leakiness was interpreted as a consequence of in-phase reinitiation at the site of the frameshift mutation (3). More recently (7), however, a set of 100 Escherichia coli mutants, presumably frameshift because they were induced by ICR-191D, were selected for their inability to grow on lactose; 50% of them carried a defective 3-galactosidase (coded for by the z gene of the lac operon). Surprisingly, several of these z mutants were not strictly Lap-on a minimal lactose plate (7). Only the nonleaky strains were studied further; 31 of them were mapped, and were shown to be frameshift mutants by several criteria (7).We wanted to verify the presumed absence of f3-galactosiAbbreviations: dase activity in these 31 strains by using a test more sensitive than ability to grow on lactose. 16 Mutants, scattered throughout the z gene (see Fig. 1), were chosen and tested on minimal glycerol plates containing 1 mg of 5-bromo-4-chloro-3-indolyl-,B-D-galactoside and 0.24 mg of IPTG (isopropyl-,3-D-thiogalactoside) per plate. Upon incubation at 370, the colonies of all the 16 strains tested aquired a more-or lessintense blue color (after 1-5 incubation days), showing that all the colonies were able to hydrolyse 5-bromo-4-chloro-3-indolyl-f3-D-galactoside at different rates. By contrast, no color appeared, even after 10 days, with strains CP179 (lac deletion X74) or CA7033 (lac pro deletio...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Low Activity of β-Galactosidase in Frameshift Mutants of Escherichia coli

Atkins

Elseviers

Gorini

1972

Proc. Natl. Acad. Sci. U.S.A.

107

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“…Although it was hypothesized almost 50 years ago that the triplet genetic code was immutable, the identification of mutagen-induced genomic insertions that still yielded the expression of the correct protein implied otherwise (6)(7)(8). This alternative reading of mRNA indicated that the ribosome had the ability to decode a nontriplet reading frame under certain circumstances.…”

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confidence: 99%

Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops

Maehigashi

Dunkle

Miles

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

104

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Maintenance of the correct reading frame on the ribosome is essential for accurate protein synthesis. Here, we report structures of the 70S ribosome bound to frameshift suppressor tRNA SufA6 and N1-methylguanosine at position 37 (m 1 G37) modification-deficient anticodon stem loop Pro , both of which cause the ribosome to decode 4 rather than 3 nucleotides, resulting in a +1 reading frame. Our results reveal that decoding at +1 suppressible codons causes suppressor tRNA SufA6 to undergo a rearrangement of its 5′ stem that destabilizes U32, thereby disrupting the conserved U32-A38 base pair. Unexpectedly, the removal of the m 1 G37 modification of tRNA Pro also disrupts U32-A38 pairing in a structurally analogous manner. The lack of U32-A38 pairing provides a structural correlation between the transition from canonical translation and a +1 reading of the mRNA. Our structures clarify the molecular mechanism behind suppressor tRNA-induced +1 frameshifting and advance our understanding of the role played by the ribosome in maintaining the correct translational reading frame.near cognate | processivity T he three polymerase reactions of DNA replication, RNA transcription, and protein translation are essential to life and all involve a delicate balance between speed and fidelity. The bacterial ribosome decodes three mRNA nucleotides into a single amino acid at a rate of ∼20 residues/s with high fidelity (10 3

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“…Known suppressors of the frameshift mutation hisC3072 induce frameshifting that is only 1% efficient but can be isolated as His ϩ clones after 48 h of incubation at 37°C (35). The hisD3018 allele is suppressed by the sufB2 frameshift suppressor, also operating with an efficiency of only 1% (44), and such His ϩ clones are detected after 24 h of incubation at 37°C (data not shown). Thus, the His ϩ selection method used here will detect suppressor mutants with the suppression efficiency of only a fraction of a percent.…”

Section: Methodsmentioning

confidence: 99%

Alterations in the Two Globular Domains or in the Connecting α-Helix of Bacterial Ribosomal Protein L9 Induces +1 Frameshifts

Leipuviene

Björk

2007

J Bacteriol

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The ribosomal 50S subunit protein L9, encoded by the gene rplI, is an elongated protein with an ␣-helix connecting the N-and C-terminal globular domains. We isolated rplI mutants that suppress the ؉1 frameshift mutation hisC3072 in Salmonella enterica serovar Typhimurium. These mutants have amino acid substitutions in the N-terminal domain (G24D) or in the C-terminal domain (I94S, A102D, G126V, and F132S) of L9. In addition, different one-base deletions in rplI altered either the final portion of the C terminus or removed the C-terminal domain with or without the connecting ␣-helix. An alanine-to-proline substitution at position 59 (A59P), which breaks the ␣-helix between the globular domains, induced ؉1 frameshifting, suggesting that the geometrical relationship between the N and C domains is important to maintain the reading frame. Except for the alterations G126V in the C terminus and A59P in the connecting ␣-helix, our results confirm earlier results obtained by using the phage T4 gene 60-based system to monitor bypassing. The way rplI mutations suppress various frameshift mutations suggests that bypassing of many codons from several takeoff and landing sites occurred instead of a specific frameshift forward at overlapping codons.

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Restoration of In-phase Translation by an Unlinked Suppressor of a Frameshift Mutation in Salmonella typhimurium

Cited by 56 publications

References 17 publications

Low Activity of β-Galactosidase in Frameshift Mutants of Escherichia coli

Low Activity of β-Galactosidase in Frameshift Mutants of Escherichia coli

Structural insights into +1 frameshifting promoted by expanded or modification-deficient anticodon stem loops

Alterations in the Two Globular Domains or in the Connecting α-Helix of Bacterial Ribosomal Protein L9 Induces +1 Frameshifts

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