Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001129872400023&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1038/s41467-023-42689-2
eISSN
2041-1723
Externe Identifier
  • Clarivate Analytics Document Solution ID: DC6M5
  • PubMed Identifier: 37903771
Ausgabe der Veröffentlichung
1
Zeitschrift
NATURE COMMUNICATIONS
Artikelnummer
ARTN 6931
Datum der Veröffentlichung
2023
Status
Published
Titel
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Sub types
  • Article
Ausgabe der Zeitschrift
14

Data source: Web of Science (Lite)

Other metadata sources:
Abstract
<jats:title>Abstract</jats:title><jats:p>Genetic code expansion (GCE) reprograms the translational machinery to site-specifically incorporate noncanonical amino acids (ncAAs) into a selected protein. The efficiency of GCE in mammalian cells might be compromised by cellular stress responses, among which, the protein kinase R(PKR)-dependent eIF2α phosphorylation pathway can reduce translation rates. Here we test several strategies to engineer the eIF2α pathway and boost the rate of translation and show that such interventions increase GCE efficiency in mammalian cells. In particular, addition of the N-terminal PKR fragment (1–174) provides a substantial enhancement in cytoplasmic GCE and also in GCE realized by OTOs (orthogonally translating designer organelles), which built on the principle of 2D phase separation to enable mRNA-selective ncAA incorporation. Our study demonstrates an approach for improving the efficiency of GCE and provides a means by which the power of designer organelles can be further optimized to tune protein translation.</jats:p>
Autoren
DOI
10.1038/s41467-023-42689-2
eISSN
2041-1723
Ausgabe der Veröffentlichung
1
Zeitschrift
Nature Communications
Sprache
en
Artikelnummer
6931
Online publication date
2023
Status
Published online
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1038/s41467-023-42689-2
Datum der Datenerfassung
2023
Titel
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Ausgabe der Zeitschrift
14

Data source: Crossref

Abstract
Genetic code expansion (GCE) reprograms the translational machinery to site-specifically incorporate noncanonical amino acids (ncAAs) into a selected protein. The efficiency of GCE in mammalian cells might be compromised by cellular stress responses, among which, the protein kinase R(PKR)-dependent eIF2α phosphorylation pathway can reduce translation rates. Here we test several strategies to engineer the eIF2α pathway and boost the rate of translation and show that such interventions increase GCE efficiency in mammalian cells. In particular, addition of the N-terminal PKR fragment (1-174) provides a substantial enhancement in cytoplasmic GCE and also in GCE realized by OTOs (orthogonally translating designer organelles), which built on the principle of 2D phase separation to enable mRNA-selective ncAA incorporation. Our study demonstrates an approach for improving the efficiency of GCE and provides a means by which the power of designer organelles can be further optimized to tune protein translation.
Addresses
  • Biocenter, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 17, 55128, Mainz, Germany.
Autoren
DOI
10.1038/s41467-023-42689-2
eISSN
2041-1723
Externe Identifier
  • PubMed Identifier: 37903771
  • PubMed Central ID: PMC10616097
Open access
true
ISSN
2041-1723
Ausgabe der Veröffentlichung
1
Zeitschrift
Nature communications
Schlüsselwörter
  • Animals
  • Mammals
  • Protein Kinases
  • Amino Acids
  • Proteins
  • Phosphorylation
  • Genetic Code
Sprache
eng
Medium
Electronic
Online publication date
2023
Open access status
Open Access
Paginierung
6931
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells.
Sub types
  • Research Support, Non-U.S. Gov't
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
14

Files

https://www.nature.com/articles/s41467-023-42689-2.pdf https://europepmc.org/articles/PMC10616097?pdf=render

Data source: Europe PubMed Central

Abstract
Genetic code expansion (GCE) reprograms the translational machinery to site-specifically incorporate noncanonical amino acids (ncAAs) into a selected protein. The efficiency of GCE in mammalian cells might be compromised by cellular stress responses, among which, the protein kinase R(PKR)-dependent eIF2α phosphorylation pathway can reduce translation rates. Here we test several strategies to engineer the eIF2α pathway and boost the rate of translation and show that such interventions increase GCE efficiency in mammalian cells. In particular, addition of the N-terminal PKR fragment (1-174) provides a substantial enhancement in cytoplasmic GCE and also in GCE realized by OTOs (orthogonally translating designer organelles), which built on the principle of 2D phase separation to enable mRNA-selective ncAA incorporation. Our study demonstrates an approach for improving the efficiency of GCE and provides a means by which the power of designer organelles can be further optimized to tune protein translation.
Date of acceptance
2023
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37903771
DOI
10.1038/s41467-023-42689-2
eISSN
2041-1723
Externe Identifier
  • PubMed Central ID: PMC10616097
Ausgabe der Veröffentlichung
1
Zeitschrift
Nat Commun
Schlüsselwörter
  • Animals
  • Genetic Code
  • Proteins
  • Amino Acids
  • Phosphorylation
  • Protein Kinases
  • Mammals
Sprache
eng
Country
England
Paginierung
6931
PII
10.1038/s41467-023-42689-2
Datum der Veröffentlichung
2023
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Titel
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
14

Data source: PubMed

Author's licence
CC-BY
Autoren
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.1038/s41467-023-42689-2
File(s) embargoed
false
Open access
true
ISSN
2041-1723
Zeitschrift
Nature Communications
Schlüsselwörter
  • 570 Biowissenschaften
  • 570 Life sciences
Sprache
eng
Open access status
Open Access
Paginierung
6931
Datum der Veröffentlichung
2023
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/9805
Herausgeber
Nature Publishing Group UK
Datum der Datenerfassung
2023
Datum, an dem der Datensatz öffentlich gemacht wurde
2023
Zugang
Public
Titel
Remodeling the cellular stress response for enhanced genetic code expansion in mammalian cells
Ausgabe der Zeitschrift
14

Files

remodeling_the_cellular_stres-20231211120849893.pdf

Data source: OPENSCIENCE.UB

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