Equipe d’Accueil : “RNA and protein modifications”

Intitulé de l’Unité : Laboratoire de Biologie Structurale de la Cellule (CNRS UMR 7654)

Nom du Responsable de l’Unité : Dr Emmanuelle SCHMITT

Nom du Responsable de l’Équipe : Dr Marc GRAILLE

Adresse : Ecole Polytechnique, Route de Saclay 91120 PALAISEAU

Responsable de l’encadrement : Dr Marc GRAILLE

Tél : 01 69 33 48 90  Fax : ……………………… E-mail:  marc.graille@polytechnique.edu

Website : https://bioc.ip-paris.fr/en/research/rna-and-protein-modifications

Résumé du projet (environ une demi-page)

Most RNAs involved in translation—including tRNAs, mRNAs, and rRNAs—undergo numerous and diverse chemical modifications. These modifications contribute to the efficiency, fidelity, and regulation of protein synthesis. For a long time, their biological roles were largely overlooked, often due to the absence of strong phenotypes in single-cell organisms lacking the corresponding modification enzymes (also known as “writers”), or because many of these writers remain unidentified. However, over the past decade, increasing evidence has highlighted the critical functions of these modifications, notably in cancer and neurological development. For instance, mutations in several tRNA-modifying enzymes have been linked to neurological disorders.

This Master’s research project aims to investigate the role of a specific tRNA modification enzyme in protein synthesis and cell migration. The selected student will build on ongoing work within our team, which has shown that loss of function of this enzyme alters the expression levels of various proteins, including some involved in cell migration and post-translational modifications.

The primary goal is to determine whether the effects on protein expression are due to the presence of the enzyme itself or its catalytic activity. To address this, human cells depleted of the enzyme (already available in the lab) will be transfected with plasmids encoding either the wild-type protein or a catalytically inactive mutant. The expression levels of target proteins will be assessed. Additionally, the regulation of these proteins at the post-transcriptional (via RT-qPCR) or translational level (via ribosome profiling, in collaboration with a partner lab) will be evaluated.

The project also includes assessing the role of this tRNA modification enzyme in cell migration, in partnership with another team from our research unit.

Throughout the internship, the student will gain hands-on experience with various techniques in molecular and cell biology, including human cell culture, transfection, protein extraction, western blotting, RT-qPCR, RNA purification, and mass spectrometry-based detection and analysis of RNA modifications.

This project will contribute to understanding how chemical modifications on the tRNA body can influence protein expression. Ideally, the student will apply for a PhD fellowship through the Institut Polytechnique graduate school.

Host Laboratory

The internship will take place in the Laboratory of Structural Biology of the Cell, located at the École Polytechnique campus (CNRS, Institut Polytechnique de Paris) in Palaiseau, France—less than one hour by RER B from central Paris.

Our international and dynamic research team focuses on understanding how RNA modifications are deposited and how they influence RNA translation, decay, cell proliferation, and organ development.

Dernières Publications en lien avec le projet :

  • Wang C; Tay LLE; Hu W; Corre M; Graille M. (2025) TRMT112, a master activator of several methyltransferases modifying factors involved in RNA maturation and translation. Frontiers in RNA Research; DOI : 3389/frnar.2025.1556979.
  • Wang, C.; Ulryck, N.; Herzel, L.; Pythoud, N.; Kleiber, N.; Guérineau, V.; Jactel, V.; Moritz, C.; Bohnsack, M.; Carapito, C.; Touboul, D.; Bohnsack, K.E.; Graille, M. (2023), N2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing. Nucleic Acids Res, 51(14), 7496-
  • Wang C.; van Tran, N.; Jactel V.; Guerineau V.; Graille M. (2020), Structural and functional insights into Archaeoglobus fulgidus m2G10 tRNA methyltransferase Trm11 and its Trm112 activator. Nucleic Acids Res, 48(19); 11068-11082.
  • Leismann; Spagnuolo M.; Pradhan M.; Wacheul L.; Vu M.A.; Musheev M.; Mier P.; Andrade-Navarro M.A.; Graille M.; Niehrs C.; Lafontaine D.L.J.; Roignant J.Y. (2020), The 18S ribosomal RNA m6A methyltransferase Mettl5 is required for normal walking behavior in Drosophila. Embo reports, 21(7); e49443.
  • van Tran ; Ernst, F.G.M.; Hawley, B.R.; Zorbas, C.; Ulryck, N.; Hackert, P.; Bohnsack, K.E.; Bohnsack M.T.; Jaffrey, S.R.; Graille M.; Lafontaine D.L.J.. (2019), The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112. Nucleic Acids Res, 47(15); 7719-7733

Ce projet s’inscrit dans la perspective d’une thèse 

type de financement prévu : Bourse de thèse de l’ED de l’institut Polytechnique de Paris (ED 626)

 Ecole Doctorale de rattachement : ED de l’institut Polytechnique de Paris (ED 626)