Structural Basis for Bacterial Ribosome-Associated Quality Control by RqcH and RqcP

Crowe‐McAuliffe, Caillan; Takada, Hiraku; Murina, Victoriia; Polte, Christine; Kasvandik, Sergo; Tenson, Tanel; Ignatova, Zoya; Atkinson, Gemma C.; Wilson, Daniel N.; Hauryliuk, Vasili

doi:10.1016/j.molcel.2020.11.002

Cited by 49 publications

(105 citation statements)

References 84 publications

(103 reference statements)

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“…RqcH is a homolog of the eukaryotic RQC factor Rqc2/NEMF (recently reviewed by Joazeiro, 2019 andZaher, 2019). These factors have a conserved core domain architecture of NFACT-N (NFACT means domain found in NEMF, FbpA, Caliban, and Tae2), helix-hairpin-helix (HhH), coiled coils (CC), a globular middle (M)-domain between the two helices of the CC, and an NFACT-R domain (Burroughs and Aravind, 2014;Shao et al, 2015;Shen et al, 2015;Lytvynenko et al, 2019;Crowe-McAuliffe et al, 2021). Eukaryotic NEMF proteins typically contain an additional NFACT-C domain of unknown function (Burroughs and Aravind, 2014).…”

Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

“…Eukaryotic NEMF proteins typically contain an additional NFACT-C domain of unknown function (Burroughs and Aravind, 2014). Recently, two groups have analyzed bacterial RQC by cryo-EM, using samples prepared by immunoprecipitation of a FLAG-tagged RqcH in B. subtilis (Crowe-McAuliffe et al, 2021;Filbeck et al, 2021;highlighted by Brandman and Frost, 2021). In both structures, RqcH was bound to the large subunit-P-tRNA-nascent chain complex, straddling the central protuberance (CP) and the L7/L12 stalk, similarly to what was observed in low-resolution reconstructions of eukaryotic NEMF proteins (Shao et al, 2015;Shen et al, 2015).…”

Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

“…RqcP was seen to bind between H69 of the 23S rRNA, the anticodon stem of the P-tRNA and the NFACT-N domain of RqcH (Figure 5A). RqcP co-precipitates RqcH, and is required for alanine tailing (Crowe-McAuliffe et al, 2021;Filbeck et al, 2021).…”

Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

“…The bacterial RQC pathway was discovered originally in B. subtilis (Figures 1D,E) and is partially redundant with transtranslation (Lytvynenko et al, 2019). Similar to eukaryotic RQC (reviewed by Joazeiro, 2019 andZaher, 2019), bacterial RQC acts on large subunits bearing peptidyl-tRNAs, tagging and targeting the aberrant nascent peptide for degradation, thereby freeing and recycling the large subunit for the next round of translation (Lytvynenko et al, 2019;Crowe-McAuliffe et al, 2021;Filbeck et al, 2021). Bacterial RQC involves RqcH, a NEMF-family protein and homolog of the eukaryotic RQC factor Rqc2.…”

Section: Introductionmentioning

confidence: 99%

“…NEMF family proteins are also found in archaea, although they have been lost in a few bacterial lineages, including E. coli. The near-universal phylogenetic distribution of the factor, as well as its conserved domain organization, structure and the functional similarity between prokaryotic RqcH and eukaryotic Rqc2/NEMF imply that the factor was already present in the last common universal ancestor (LUCA) (Burroughs and Aravind, 2014;Lytvynenko et al, 2019;Crowe-McAuliffe et al, 2021). At present, the relationship between RQC and other bacterial ribosome rescue systems remains unclear, mainly due to the lack of direct information as to which factor and/or conditions generate the peptidyl-tRNA-large subunit complexes.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

Section: Bacterial Ribosome-associated Quality Controlmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ribosome Rescue Pathways in Bacteria

2021

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Molecular Highway Patrol for Ribosome Collisions

et al. 2023

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During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions.

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Physiology of trans‐translation deficiency in Bacillus subtilis – a comparative proteomics study

et al. 2023

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Abstracttrans‐Translation is the most effective ribosome rescue system known in bacteria. While it is essential in some bacteria, Bacillus subtilis possesses two additional alternative ribosome rescue mechanisms that require the proteins BrfA or RqcH. To investigate the physiology of trans‐translation deficiency in the model organism B. subtilis, we compared the proteomes of B. subtilis 168 and a ΔssrA mutant in the mid‐log phase using gel‐free label‐free quantitative proteomics. In chemically defined medium, the growth rate of the ssrA deletion mutant was 20% lower than that of B. subtilis 168. An 35S‐methionine incorporation assay demonstrated that protein synthesis rates were also lower in the ΔssrA strain. Alternative rescue factors were not detected. Among the 34 proteins overrepresented in the mutant strain were eight chemotaxis proteins. Indeed, both on LB agar and minimal medium the ΔssrA strain showed an altered motility and chemotaxis phenotype. Despite the lower growth rate, in the mutant proteome ribosomal proteins were more abundant while proteins related to amino acid biosynthesis were less abundant than in the parental strain. This overrepresentation of ribosomal proteins coupled with a lower protein synthesis rate and down‐regulation of precursor supply reflects the slow ribosome recycling in the trans‐translation‐deficient mutant.

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Structural Basis for Bacterial Ribosome-Associated Quality Control by RqcH and RqcP

Cited by 49 publications

References 84 publications

Ribosome Rescue Pathways in Bacteria

Ribosome Rescue Pathways in Bacteria

Molecular Highway Patrol for Ribosome Collisions

Physiology of trans‐translation deficiency in Bacillus subtilis – a comparative proteomics study

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