Resuming translation on tmRNA: a unique mode of determining a reading frame

Williams, Kelly P.; Martindale, Kimberly A.; Bartel, David P.

doi:10.1093/emboj/18.19.5423

Cited by 95 publications

(117 citation statements)

References 32 publications

(46 reference statements)

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“…The protection of some nucleotides in this region has also been seen for the SmpBtmRNA complex in solution (33). Moreover, a number of mutations in this region either inactivate or affect trans-translation (34)(35)(36)47). Our model allows SmpB interactions with the ribosomal A-site as it was recently proposed (48).…”

Section: Introductionsupporting

confidence: 63%

“…Mutations in this sequence lead either to complete loss of tmRNA function or to shifts in the reading frame (34)(35)(36). Recently, direct connection between SmpB and the upstream sequence in establishing the reading frame on tmRNA has been demonstrated (37).…”

Section: Introductionmentioning

confidence: 99%

“…A number of biochemical data support this hypothesis. The A79-A86 loop has been shown to be essential for correct resume codon positioning (34,35). Moreover, a mutation at position 86 allows for peptidyl transfer, but not for further translocation (33).…”

Section: Introductionmentioning

confidence: 99%

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Structural aspects of trans‐translation

et al. 2010

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Summarytrans-Translation is a process which the bacterial cells apply to rescue the ribosomes that are arrested during the translation of damaged mRNA and to get rid of the mRNA and the product polypeptide. In the course of trans-translation, the mRNAlike domain of tmRNA replaces the nonstop messenger RNA bound to the ribosome. Although several structural elements of tmRNA and SmpB known to be essential for correct determination of resume codon, the molecular mechanism of trans-translation is not well understood. Computer modeling has been used to develop a model for the spatial organization of the tmRNA inside the ribosome at different stages of trans-translation leading to a proposal for the mechanism of the templateswitching process.

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Section: Introductionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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Structural aspects of trans‐translation

et al. 2010

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“…X91 strain (⌬ssrA) (20) was a kind gift of Dr. K. Williams. The SKZ-1 strain of E. coli with disrupted tmRNA gene and thermosensitive RF2 was made and used for the isolation of tmRNA⅐ribosome complex as follows.…”

Section: Methodsmentioning

confidence: 99%

Stepping Transfer Messenger RNA through the Ribosome

Shpanchenko

Zvereva

Ivanov

et al. 2005

Journal of Biological Chemistry

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“…Interestingly, the first amino acid (Ala) of the short peptide encoded by the resume codon GCN is evolutionarily conserved across the tmRNA sequences from different species. In addition, although the ssrA mutants harboring alternate resume codons have been studied (24,34), the reasons for its high conservation are not understood.…”

mentioning

confidence: 99%

Functional Significance of an Evolutionarily Conserved Alanine (GCA) Resume Codon in tmRNA in Escherichia coli

Kapoor¹,

Samhita²,

Varshney³

2011

Journal of Bacteriology

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Occasionally, ribosomes stall on mRNAs prior to the completion of the polypeptide chain. In Escherichia coli and other eubacteria, tmRNA-mediated trans-translation is a major mechanism that recycles the stalled ribosomes. The tmRNA possesses a tRNA-like domain and a short mRNA region encoding a short peptide (ANDENYALAA in E. coli) followed by a termination codon. The first amino acid (Ala) of this peptide encoded by the resume codon (GCN) is highly conserved in tmRNAs in different species. However, reasons for the high evolutionary conservation of the resume codon identity have remained unclear. In this study, we show that changing the E. coli tmRNA resume codon to other efficiently translatable codons retains efficient functioning of the tmRNA. However, when the resume codon was replaced with the low-usage codons, its function was adversely affected. Interestingly, expression of tRNAs decoding the low-usage codon from plasmid-borne gene copies restored efficient utilization of tmRNA. We discuss why in E. coli, the GCA (Ala) is one of the best codons and why all codons in the short mRNA of the tmRNA are decoded by the abundant tRNAs.Occasionally, during the process of translation, ribosomes stall on mRNAs prior to the completion of the polypeptide chain. If not recycled, accumulation of the stalled ribosomes is detrimental to the organism as it sequesters not only the ribosomes but also the tRNAs (as peptidyl-tRNAs) and brings protein synthesis to a halt. In Escherichia coli and other eubacteria, a well-known pathway that recycles the stalled ribosomes utilizes tmRNA (SsrA or 10Sa RNA) by a process called trans-translation (18,36). The tmRNA contains a tRNA like domain and an mRNA region encoding a short peptide (AN DENYALAA in E. coli) followed by a termination codon (Fig. 1A). The tmRNA is aminoacylated with alanine (in its tRNAlike domain) and recruited to the A-site of the ribosome stalled on a truncated mRNA. The polypeptide from the P-site tRNA is transferred to the alanine on the tRNA-like domain of tm-RNA to form (peptidyl)-alanyl-tmRNA. The ribosome then resumes translation (trans-translation) decoding the first codon (the "resume codon") and the remaining codons of the short open reading frame in the tmRNA. When the termination codon in the tmRNA reaches the ribosomal A-site, the C-terminally tagged polypeptide is released. Thus, the process of trans-translation in E. coli appends AANDENYALAA sequence to the incomplete polypeptide and marks it for degradation by cellular proteases. The C-terminal amino acids in the appended sequence are important for recognition by the cellular proteases; and while the tmRNA mutants that encode ANDENYALDD or ANDEHHHHHH rescue the stalled ribosomes, they do not direct the tagged proteins to degradation (9,11,17,25). Interestingly, the first amino acid (Ala) of the short peptide encoded by the resume codon GCN is evolutionarily conserved across the tmRNA sequences from different species. In addition, although the ssrA mutants harboring alternate resume codons have been...

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Resuming translation on tmRNA: a unique mode of determining a reading frame

Cited by 95 publications

References 32 publications

Structural aspects of trans‐translation

Structural aspects of trans‐translation

Stepping Transfer Messenger RNA through the Ribosome

Functional Significance of an Evolutionarily Conserved Alanine (GCA) Resume Codon in tmRNA in Escherichia coli

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