Horizontal gene transfer of a key translation protein has shaped the polyproline proteome

Brewer, Tess E.; Wagner, Andreas

doi:10.1101/2023.10.19.563058

Cited by 3 publications

(5 citation statements)

References 51 publications

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“…The ValS tRNA synthetase is also of interest since it contains a polyproline motif that is highly conserved across eukaryotic, archaeal, and bacterial proteomes (65). It has been proposed that EF-P is universally conserved, in part, to efficiently translate this protein (65, 66).…”

Section: Discussionmentioning

confidence: 99%

YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

Hong¹,

Prince²,

Wu³

et al. 2023

Preprint

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Protein synthesis is catalyzed by the ribosome and a host of highly conserved elongation factors. Most elongation factors that are conserved in all domains of life are essential, such as EF-Tu (e/aEF1A) and EF-G (e/aEF2). In contrast, the universally conserved elongation factor P (EF-P/eIF5A) is essential in eukaryotes but is dispensable in most bacteria. EF-P prevents ribosome stalling at difficult-to translate sequences, especially polyprolines. Since efp deletion phenotypes range from modest to lethal in different bacterial species, we hypothesized that some bacteria encode an uncharacterized elongation factor with compensatory functions. To identify this factor, we used Tn-seq to screen for genes that are essential in the absence of EF-P in Bacillus subtilis. This screen identified YfmR, a member of the ABCF family of ATPases, as a translation factor that is essential when efp is deleted. We find that depleting YfmR from ∆efp cells decreases actively translating ribosomes and increases free ribosomal subunits bound to initiator tRNA, suggesting that ribosomes stall in early elongation. We also find that deleting efp from the spore-forming pathogen Bacillus anthracis causes a severe survival defect in liquid culture and in the presence of macrophages. B. anthracis ∆efp also does not produce detectable spores. We find that heterologous expression of B. subtilis YfmR in B. anthracis ∆efp cells partially rescues the severe growth and sporulation defects of this mutant. Our results therefore identify YfmR as an important translation factor that becomes essential in the absence of EF-P, and suggest that the essential function of YfmR and EF-P is to assist translation during early elongation.

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Section: Discussionmentioning

confidence: 99%

YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

Hong¹,

Prince²,

Wu³

et al. 2023

Preprint

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“…Third, EfpLs predominantly co-occur with the EF-P subfamily activated by EpmA whereas the presence of an EarP-type efp in the genome typically excludes the existence of the paralogous EfpL ( Supplementary Fig. S1C ) 23 . Lastly, distinguishing itself from all other EF-Ps, EfpL appears to possess a β3Ωβ4 extension ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Starting with the catalytic residue at the loop tip, which is not restricted to lysine as for eukaryotes/archaea. Instead, one also finds asparagine, glutamine, methionine, serine and glycine, besides arginine 23 . These changes extend to the overall sequence composition of β3Ωβ4 to either increase stiffness 66 or, in the case of EfpL, to prolong the loop, as shown in this study by the first EfpL high-resolution structure.…”

Section: Discussionmentioning

confidence: 99%

“…Using HMMER v.3.4 searches we identified these proteins in 1230 and 565 genomes, respectively. Orthologs of the YmfI protein (Uniprot ID: O31767) from Bacillus subtilis 20,65 were obtained using the procedure described in Brewer and Wagner 23 .…”

Section: Methodsmentioning

confidence: 99%

“…1A; Extended Data Fig. 1 ) 14,23 suggesting that its role in translation diverges from those of canonical EF-Ps. However, to date the molecular function of EfpL remains enigmatic.…”

Section: Introductionmentioning

confidence: 99%

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EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences

Sieber,

Parr,

von Ehr

et al. 2024

Preprint

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Polyproline sequences (XPPX) stall ribosomes, thus being deleterious for all living organisms. In bacteria, translation elongation factor P (EF-P) plays a crucial role in overcoming such arrests. 12% of eubacteria possess an EF-P paralog - YeiP (EfpL) of unknown function. Here, we functionally and structurally characterize EfpL from Escherichia coli and demonstrate its yet unrecognized role in the translational stress response. Through ribosome profiling, we analyzed the EfpL arrest motif spectrum and discovered additional stalls beyond the canonical XPPX motifs at single-proline sequences (XPX), that both EF-P and EfpL can resolve. Notably, the two factors can also induce pauses. We further report that, contrary to the housekeeping EF-P, EfpL can sense the metabolic state of the cell, via lysine acylation. Together, our work uncovers a new player in ribosome rescue at proline-containing sequences, and provides evidence that co-occurrence of EF-P and EfpL is an evolutionary driver for higher bacterial growth rates.

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YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

Hong,

Prince,

Tetreault

et al. 2024

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

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Protein synthesis is performed by the ribosome and a host of highly conserved elongation factors. Elongation factor P (EF-P) prevents ribosome stalling at difficult-to-translate sequences, such as polyproline tracts. In bacteria, phenotypes associated with efp deletion range from modest to lethal, suggesting that some species encode an additional translation factor that has similar function to EF-P. Here we identify YfmR as a translation factor that is essential in the absence of EF-P in Bacillus subtilis . YfmR is an ABCF ATPase that is closely related to both Uup and EttA, ABCFs that bind the ribosomal E-site and are conserved in more than 50% of bacterial genomes. We show that YfmR associates with actively translating ribosomes and that depleting YfmR from Δ efp cells causes severe ribosome stalling at a polyproline tract in vivo. YfmR depletion from Δ efp cells was lethal and caused reduced levels of actively translating ribosomes. Our results therefore identify YfmR as an important translation factor that is essential in B. subtilis in the absence of EF-P.

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Horizontal gene transfer of a key translation protein has shaped the polyproline proteome

Cited by 3 publications

References 51 publications

YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences

YfmR is a translation factor that prevents ribosome stalling and cell death in the absence of EF-P

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