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

Abstract Polyproline sequences are deleterious to cells because they stall ribosomes. In bacteria, EF-P plays an important role in overcoming such polyproline sequence-induced ribosome stalling. Additionally, numerous bacteria possess an EF-P paralog called EfpL (also known as YeiP) of unknown funct...

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Main Authors: Alina Sieber, Marina Parr, Julian von Ehr, Karthikeyan Dhamotharan, Pavel Kielkowski, Tess Brewer, Anna Schäpers, Ralph Krafczyk, Fei Qi, Andreas Schlundt, Dmitrij Frishman, Jürgen Lassak
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54556-9
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author Alina Sieber
Marina Parr
Julian von Ehr
Karthikeyan Dhamotharan
Pavel Kielkowski
Tess Brewer
Anna Schäpers
Ralph Krafczyk
Fei Qi
Andreas Schlundt
Dmitrij Frishman
Jürgen Lassak
author_facet Alina Sieber
Marina Parr
Julian von Ehr
Karthikeyan Dhamotharan
Pavel Kielkowski
Tess Brewer
Anna Schäpers
Ralph Krafczyk
Fei Qi
Andreas Schlundt
Dmitrij Frishman
Jürgen Lassak
author_sort Alina Sieber
collection DOAJ
description Abstract Polyproline sequences are deleterious to cells because they stall ribosomes. In bacteria, EF-P plays an important role in overcoming such polyproline sequence-induced ribosome stalling. Additionally, numerous bacteria possess an EF-P paralog called EfpL (also known as YeiP) of unknown function. Here, we functionally and structurally characterize EfpL from Escherichia coli and demonstrate its role in the translational stress response. Through ribosome profiling, we analyze the EfpL arrest motif spectrum and find additional sequences beyond the canonical polyproline motifs that both EF-P and EfpL can resolve. Notably, the two factors can also induce pauses. We further report that EfpL can sense the metabolic state of the cell via lysine acylation. Overall, our work characterizes the role of EfpL 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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issn 2041-1723
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series Nature Communications
spelling doaj-art-2fbdff9fdc5643b6bfb2161f50fa26ba2024-12-08T12:35:45ZengNature PortfolioNature Communications2041-17232024-12-0115111610.1038/s41467-024-54556-9EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequencesAlina Sieber0Marina Parr1Julian von Ehr2Karthikeyan Dhamotharan3Pavel Kielkowski4Tess Brewer5Anna Schäpers6Ralph Krafczyk7Fei Qi8Andreas Schlundt9Dmitrij Frishman10Jürgen Lassak11Faculty of Biology, Microbiology, Ludwig-Maximilians-Universität MünchenDepartment of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität MünchenInstitute for Molecular Biosciences and Biomolecular Resonance Center (BMRZ), Goethe University FrankfurtInstitute for Molecular Biosciences and Biomolecular Resonance Center (BMRZ), Goethe University FrankfurtDepartment of Chemistry, Institut für Chemische Epigenetik (ICEM), Ludwig-Maximilians-Universität MünchenFaculty of Biology, Microbiology, Ludwig-Maximilians-Universität MünchenFaculty of Biology, Microbiology, Ludwig-Maximilians-Universität MünchenFaculty of Biology, Microbiology, Ludwig-Maximilians-Universität MünchenState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen UniversityInstitute for Molecular Biosciences and Biomolecular Resonance Center (BMRZ), Goethe University FrankfurtDepartment of Bioinformatics, Wissenschaftszentrum Weihenstephan, Technische Universität MünchenFaculty of Biology, Microbiology, Ludwig-Maximilians-Universität MünchenAbstract Polyproline sequences are deleterious to cells because they stall ribosomes. In bacteria, EF-P plays an important role in overcoming such polyproline sequence-induced ribosome stalling. Additionally, numerous bacteria possess an EF-P paralog called EfpL (also known as YeiP) of unknown function. Here, we functionally and structurally characterize EfpL from Escherichia coli and demonstrate its role in the translational stress response. Through ribosome profiling, we analyze the EfpL arrest motif spectrum and find additional sequences beyond the canonical polyproline motifs that both EF-P and EfpL can resolve. Notably, the two factors can also induce pauses. We further report that EfpL can sense the metabolic state of the cell via lysine acylation. Overall, our work characterizes the role of EfpL 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.https://doi.org/10.1038/s41467-024-54556-9
spellingShingle Alina Sieber
Marina Parr
Julian von Ehr
Karthikeyan Dhamotharan
Pavel Kielkowski
Tess Brewer
Anna Schäpers
Ralph Krafczyk
Fei Qi
Andreas Schlundt
Dmitrij Frishman
Jürgen Lassak
EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
Nature Communications
title EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
title_full EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
title_fullStr EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
title_full_unstemmed EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
title_short EF-P and its paralog EfpL (YeiP) differentially control translation of proline-containing sequences
title_sort ef p and its paralog efpl yeip differentially control translation of proline containing sequences
url https://doi.org/10.1038/s41467-024-54556-9
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