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Riboregulation of Enolase 1 activity controls glycolysis and embryonic stem cell differentiation

Title data

Huppertz, Ina ; Perez-Perri, Joel I. ; Mantas, Panagiotis ; Sekaran, Thileepan ; Schwarzl, Thomas ; Russo, Francesco ; Ferring-Appel, Dunja ; Koskova, Zuzana ; Dimitrova-Paternoga, Lyudmila ; Kafkia, Eleni ; Hennig, Janosch ; Neveu, Pierre A. ; Patil, Kiran ; Hentze, Matthias W.:
Riboregulation of Enolase 1 activity controls glycolysis and embryonic stem cell differentiation.
In: Molecular Cell. Vol. 82 (2022) Issue 14 . - pp. 2666-2680.
ISSN 1097-4164
DOI: https://doi.org/10.1016/j.molcel.2022.05.019

Project information

Project financing: Europäische Strukturfonds
F&E-Vereinbarung
Fritz Thyssen Stiftung für Wissenschaftsförderung
Hanns-Seidel-Stiftung
Konrad-Adenauer-Stiftung
Robert Bosch Stiftung
Studienstiftung des deutschen Volkes
Stifterverband für die deutsche Wissenschaft
VolkswagenStiftung

Abstract in another language

Differentiating stem cells must coordinate their metabolism and fate trajectories. Here, we report that the catalytic activity of the glycolytic enzyme Enolase 1 (ENO1) is directly regulated by RNAs leading to metabolic rewiring in mouse embryonic stem cells (mESCs). We identify RNA ligands that specifically inhibit ENO1's enzymatic activity in vitro and diminish glycolysis in cultured human cells and mESCs. Pharmacological inhibition or RNAi-mediated depletion of the protein deacetylase SIRT2 increases ENO1's acetylation and enhances its RNA binding. Similarly, induction of mESC differentiation leads to increased ENO1 acetylation, enhanced RNA binding, and inhibition of glycolysis. Stem cells expressing mutant forms of ENO1 that escape or hyper-activate this regulation display impaired germ layer differentiation. Our findings uncover acetylation-driven riboregulation of ENO1 as a physiological mechanism of glycolytic control and of the regulation of stem cell differentiation. Riboregulation may represent a more widespread principle of biological control.

Further data

Item Type: Article in a journal
Refereed: Yes
Keywords: Enolase 1; RNA-binding proteins; RNA-protein interactions; acetylation; cancer; embryonic stem cell differentiation; glycolysis; metabolism
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry > Chair Biochemistry with an Emphasis on Biophysical Chemistry - Univ.-Prof. Dr. Janosch Hennig
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 500 Natural sciences
500 Science > 540 Chemistry
500 Science > 570 Life sciences, biology
Date Deposited: 19 Sep 2022 07:02
Last Modified: 19 Oct 2022 13:28
URI: https://eref.uni-bayreuth.de/id/eprint/71881