A New Mechanism for Ribosome Rescue Can Recruit RF1 or RF2 to Nonstop Ribosomes

Goralski, Tyler D. P.; Kirimanjeswara, Girish S.; Keiler, Kenneth C.

doi:10.1128/mbio.02436-18

Cited by 33 publications

(31 citation statements)

References 41 publications

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“…These proteins harbor charged helical regions that recognize non-stop translational stalling events via interaction with exposed regions in the anticodon recognition site. In this regard it is has been recently reported that the ArfT protein in Francisella tularensis with a comparable charged α-helix can similarly recruit the canonical bRF-PHs, RF1/RF2, to stalled ribosomes [101]. We observed that rather than being a Francisella -specific novelty, the ArfT protein is a single representative of a broadly distributed family with sporadic representation in several bacterial lineages, and even certain archaea and eukaryotes such as fungi and plants (Figure 5B, Supplementary Data).…”

Section: Functional and Evolutionary Implicationsmentioning

confidence: 99%

The Origin and Evolution of Release Factors: Implications for Translation Termination, Ribosome Rescue, and Quality Control Pathways

Burroughs

Aravind

2019

IJMS

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The evolution of release factors catalyzing the hydrolysis of the final peptidyl-tRNA bond and the release of the polypeptide from the ribosome has been a longstanding paradox. While the components of the translation apparatus are generally well-conserved across extant life, structurally unrelated release factor peptidyl hydrolases (RF-PHs) emerged in the stems of the bacterial and archaeo-eukaryotic lineages. We analyze the diversification of RF-PH domains within the broader evolutionary framework of the translation apparatus. Thus, we reconstruct the possible state of translation termination in the Last Universal Common Ancestor with possible tRNA-like terminators. Further, evolutionary trajectories of the several auxiliary release factors in ribosome quality control (RQC) and rescue pathways point to multiple independent solutions to this problem and frequent transfers between superkingdoms including the recently characterized ArfT, which is more widely distributed across life than previously appreciated. The eukaryotic RQC system was pieced together from components with disparate provenance, which include the long-sought-after Vms1/ANKZF1 RF-PH of bacterial origin. We also uncover an under-appreciated evolutionary driver of innovation in rescue pathways: effectors deployed in biological conflicts that target the ribosome. At least three rescue pathways (centered on the prfH/RFH, baeRF-1, and C12orf65 RF-PH domains), were likely innovated in response to such conflicts.

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Section: Functional and Evolutionary Implicationsmentioning

confidence: 99%

The Origin and Evolution of Release Factors: Implications for Translation Termination, Ribosome Rescue, and Quality Control Pathways

Burroughs

Aravind

2019

IJMS

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“…Like ArfB, ArfT has a broader phylogenetic distribution ( Burroughs and Aravind, 2019 ). Interestingly, ArfT cooperates with both RF1 and RF2 for hydrolysis of the nascent chain ( Goralski et al, 2018 ). BrfA is likely limited to the Bacillus genus and exclusively recruits RF2, and hence BrfA has some similarities but also differences to ArfA ( Shimokawa-Chiba et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Ribosome Rescue Pathways in Bacteria

2021

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Ribosomes that become stalled on truncated or damaged mRNAs during protein synthesis must be rescued for the cell to survive. Bacteria have evolved a diverse array of rescue pathways to remove the stalled ribosomes from the aberrant mRNA and return them to the free pool of actively translating ribosomes. In addition, some of these pathways target the damaged mRNA and the incomplete nascent polypeptide chain for degradation. This review highlights the recent developments in our mechanistic understanding of bacterial ribosomal rescue systems, including drop-off, trans-translation mediated by transfer-messenger RNA and small protein B, ribosome rescue by the alternative rescue factors ArfA and ArfB, as well as Bacillus ribosome rescue factor A, an additional rescue system found in some Gram-positive bacteria, such as Bacillus subtilis. Finally, we discuss the recent findings of ribosome-associated quality control in particular bacterial lineages mediated by RqcH and RqcP. The importance of rescue pathways for bacterial survival suggests they may represent novel targets for the development of new antimicrobial agents against multi-drug resistant pathogenic bacteria.

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“…If the alternative rescue factors evolved more recently than the translation factors, their interactions with the translation components, such as the ribosome and an RF, might be species-specific. Indeed, F. tularensis ArfT can work with F. tularensis RF1 or RF2, but not E. coli RFs 24 . Also, E. coli ArfA fails to recruit Thermus thermophilus RF2 36,37 .…”

Section: Resultsmentioning

confidence: 99%

“…Although the physiological role of ArfB in E. coli is unknown, its homologs are widely distributed among both Gram-positive and -negative bacteria 5,20,22 , as well as eukaryotic mitochondria 23 . ArfT in Francisella tularensis , a member of γ-proteobacteria that lacks both ArfA and ArfB homologs 24 , is essential in the absence of tmRNA. Like ArfA, ArfT is an RF-dependent ribosome rescue factor, although ArfT can function with either RF1 or RF2.…”

Section: Introductionmentioning

confidence: 99%

ResQ, a release factor-dependent ribosome rescue factor in the Gram-positive bacterium Bacillus subtilis

Shimokawa-Chiba

Müller

Fujiwara

et al. 2019

Preprint

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17Rescue of the ribosomes from dead-end translation complexes, such as those on 18 truncated (non-stop) mRNA, is essential for the cell. Whereas bacteria use 19 trans-translation for ribosome rescue, some Gram-negative species possess alternative 20 and release factor (RF)-dependent rescue factors, which enable an RF to catalyze stop 21 codon-independent polypeptide release. We now discover that the Gram-positive 22Bacillus subtilis has an evolutionarily distinct ribosome rescue factor named ResQ. 23Genetic analysis shows that B. subtilis requires the function of either trans-translation or 24ResQ for growth, even in the absence of proteotoxic stresses. Biochemical and cryo-EM 25 characterization demonstrates that ResQ binds to non-stop stalled ribosomes, recruits 26 homologous RF2, but not RF1, and induces its transition into an open active 27 conformation. Although ResQ is distinct from E. coli ArfA, they use convergent 28 strategies in terms of mode of action and expression regulation, indicating that many 29 bacteria may have evolved as yet unidentified ribosome rescue systems. 30 31 round of translation initiation, a failure in termination lowers the cellular capacity of 48 protein synthesis, unless dealt with by the cellular quality control mechanisms. Indeed, a 49 loss of function in the quality control machinery leads to an accumulation of dead-end 50 translation products, which was estimated to represent ~2-4% of the translation products 51 in E. coli 3 , and results in lethality 4,5 . 52Living organisms have evolved mechanisms that resolve non-productive 53 translation complexes produced by ribosome stalling on non-stop mRNAs. Such quality 54 control is also called ribosome rescue. In eukaryotic cells, the Dom34/Hbs1 complex, 55 together with Rli1/ABCE1, mediates ribosome rescue on truncated mRNAs 4,6,7 . In 56 bacteria, two distinct mechanisms operate in the resolution of non-stop nascent 57 chain-ribosome complexes, trans-translation and stop codon-independent peptide 58 release from the ribosome 4,5,8,9 . The latter mechanism can further be classified into two 59 classes, RF-dependent and RF-independent. The crucial player in trans-translation is the 60 transfer-messenger RNA (tmRNA), which is encoded by ssrA. tmRNA cooperates with 61 SmpB, which mediates ribosomal accommodation of tmRNA at the ribosomal A-site 10,11 . 62The tmRNA is composed of tRNA-and mRNA-like domains. The former can be 63 5 charged with alanine, which then accepts the non-stop peptide and is elongated further 64 according to the mRNA-like coding function of tmRNA until the built-in stop codon is 65 reached. The result is the formation of the non-stop polypeptide bearing an extra 66 ssrA-encoded sequence (15 amino acids in B. subtilis) and dissociation of the ribosome 67 from the non-stop mRNA. The SsrA tag sequence promotes proteolytic elimination of 68 the non-stop polypeptide via targeting to cellular proteases. Trans-translation is 69 essential for the growth of some bacteria 5,12 . The essentiality lies in the liberation o...

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A New Mechanism for Ribosome Rescue Can Recruit RF1 or RF2 to Nonstop Ribosomes

Cited by 33 publications

References 41 publications

The Origin and Evolution of Release Factors: Implications for Translation Termination, Ribosome Rescue, and Quality Control Pathways

The Origin and Evolution of Release Factors: Implications for Translation Termination, Ribosome Rescue, and Quality Control Pathways

Ribosome Rescue Pathways in Bacteria

ResQ, a release factor-dependent ribosome rescue factor in the Gram-positive bacterium Bacillus subtilis

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