E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE TRANSLATION FIDELITY DURING BRAIN DEVELOPMENT

Michela Di Michele; Attina Aurore; Roux Pierre-François; Tabet Imène; Laguesse Sophie; Florido Javier; Houdeville Morane; Choquet Armelle; Encislai Betty; Arena Giuseppe; de Blasio Carlo; Wendling Olivia; Frenois Francois-Xavier; Papon Laura; Stuani Lucille; Fuentes Maryse; Jahanault-Tagliani Céline; Rousseau Mélanie; Guégan Justine; Buscail Yoan; Dupré Pierrick; Michaud Henri-Alexandre; Rodier Geneviève; Bellvert Floriant; Kulyk Hanna; Ferraro Peyret Carole; Mathieu Hugo; Close Pierre; Rapino Francesca; Chaveroux Cédric; Pirot Nelly; Rubio Lucie; Torro Adeline; Sorg Tania; Ango Fabrice; Hirtz Christophe; Compan Vincent; Lebigot Elise; Legati Andrea; Ghezzi Daniele; Nguyen Laurent; David Alexandre; Sardet Claude; Lacroix Matthieu; Le Cam Laurent

doi:10.1101/2022.12.19.521032

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E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE TRANSLATION FIDELITY DURING BRAIN DEVELOPMENT

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E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE TRANSLATION FIDELITY DURING BRAIN DEVELOPMENT

Michela Di Michele, Attina Aurore, Roux Pierre-François, Tabet Imène, Laguesse Sophie, Florido Javier, Houdeville Morane, Choquet Armelle, Encislai Betty, Arena Giuseppe, …

Nature Communications

19/12/2022

DOI: https://doi.org/10.1101/2022.12.19.521032

Abstract

SUMMARY Pyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that is relevant to LS pathogenesis. We identified the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U 34 ). E4F1-mediated direct transcriptional regulation of Dlat and Elp3 , two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensured proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlighted a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients.

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Title: E4F1 COORDINATES PYRUVATE METABOLISM AND THE ACTIVITY OF THE ELONGATOR COMPLEX TO ENSURE TRANSLATION FIDELITY DURING BRAIN DEVELOPMENT
Creators - without role: Michela Di Michele - Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier - IRCM
Attina Aurore - Université de Montpellier
Roux Pierre-François - Institut de Recherche en Cancérologie de Montpellier
Tabet Imène - Université de Montpellier
Laguesse Sophie - University of Liège
Florido Javier
Houdeville Morane
Choquet Armelle - Institut de Génomique Fonctionnelle
Encislai Betty - Institut de Recherche en Cancérologie de Montpellier
Arena Giuseppe
de Blasio Carlo - Université de Montpellier
Wendling Olivia - Inserm
Frenois Francois-Xavier - Institut universitaire du cancer de Toulouse Oncopole
Papon Laura - Institut de Recherche en Cancérologie de Montpellier
Stuani Lucille - Inserm
Fuentes Maryse - Institut Regional du Cancer de Montpellier
Jahanault-Tagliani Céline - Institut Regional du Cancer de Montpellier
Rousseau Mélanie - Institut Regional du Cancer de Montpellier
Guégan Justine - Centre National de la Recherche Scientifique
Buscail Yoan - Institut de Recherche en Cancérologie de Montpellier
Dupré Pierrick - Institut Regional du Cancer de Montpellier
Michaud Henri-Alexandre - Institut Regional du Cancer de Montpellier
Rodier Geneviève - Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier - IRCM
Bellvert Floriant
Kulyk Hanna
Ferraro Peyret Carole - Université Claude Bernard Lyon 1
Mathieu Hugo - Institut Regional du Cancer de Montpellier
Close Pierre - Institut Regional du Cancer de Montpellier
Rapino Francesca
Chaveroux Cédric - Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique
Pirot Nelly - Centre National de la Recherche Scientifique
Rubio Lucie - Institut Regional du Cancer de Montpellier
Torro Adeline - Institut Regional du Cancer de Montpellier
Sorg Tania - Institut Clinique de la Souris
Ango Fabrice - Inserm
Hirtz Christophe
Compan Vincent - Centre National de la Recherche Scientifique
Lebigot Elise - Bicêtre Hospital
Legati Andrea - Fondazione IRCCS Istituto Neurologico Carlo Besta
Ghezzi Daniele
Nguyen Laurent
David Alexandre
Sardet Claude
Lacroix Matthieu - Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier - IRCM
Le Cam Laurent - Université de Montpellier, Institut de Recherche en Cancérologie de Montpellier - IRCM
Publication Details: Nature Communications
Identifiers: 9940557109311
Academic Unit: Institut de Recherche en Cancérologie de Montpellier - IRCM
Language: English
Resource Type: Journal article
Local Fields: hal-04794212