Accéder directement au contenu

Hervé LE HIR

28
Documents

Présentation

**CURRENT POSITION Research Director, 1st class - CNRS** **Head of IBENS section "*Functional Genomics*"** **Group leader, team "*Expression of eukaryotic mRNAs*"** Institut de Biologie de l’Ecole Normale Supérieure (IBENS)– UMR8197-U1024. 46 rue d’Ulm, 75005, Paris **EDUCATION** 2006 : **HDR,** University Paris-Sud Orsay (Paris 11) 1998: **PhD, Molecular Biology,** University Paris Diderot (Paris 7) 1993 : **Master (B.A.) Biochemistry,** UPMC (Paris 6) **DISTINCTION** 2009 :**ATIP** and **ATIP+** CNRS 2010, 2014, 2019 : **P**rime d’**E**ncadrement **D**octoral et de **R**echerche CNRS **RESEARCH EXPERIENCE** **Since 2009**: Group leader of the team "*Expression of eukaryotic mRNAs*" IBENS – Section 2, Functional Genomics – Paris **2001-2008**: CR2/1 CNRS in the group of Dr. Bertrand Séraphin CGM – CNRS UPR2167 – 91190 Gif-sur-Yvette, France. **1998-2001**: Post-doctoral fellow in the lgroups of Dr. Lynne Maquat (Roswell Park Cancer Institute / Buffalo USA) and of Pr. Melissa J. Moore (HHMI / Brandeis University, MA. USA) **1993-1998**: Ph.D. (PI: Dr. Claude Thermes) – University Paris 7 CGM – CNRS UPR2167 – 91190 Gif-sur-Yvette, France. **FUNDING** **2018-2021**: **ANR blanche** – spEJCificity (Project leader) **2015-2018**: **ANR blanche** – CleaNMD (Partner, coordinator Alain Jacquier) **2014-2017**: **ANR blanche** – DifferEJnCe (Project leader) **2014-2015**: **PSL research** – (Partner, coordinator Stephan Vagner) **2014-2015**: **Association Recherche contre le Cancer** – (Project leader) **2012-2015**: **FP7 Marie Curie Initial Training Network** « RNPnet » **2012-2013**: **Fondation P.G. de Gennes** (Partner) **2011-2013**: **ANR blanche** – EJCbirth (Project leader) **2010-2013**: **Equipe FRM** (Project leader) **2010:** **Installation Nouvelle Equipe FRM** **2010-2011**: **Ligue Nationale Contre le Cancer** (Project leader) **2009-2011**: **ANR blanche** – Explore EJC (Project leader) **2009-2011**: **ATIP** CNRS **2005-2008**: **ANR blanche** – L’EJC (Project leader) **2003-2006**: **A.C.I. Jeunes Chercheurs** **2003-2004**: **France-Berkeley Fund** **Supervision activities** ========================== 1 Researcher (CR INSERM, J. Saulière) 6 PhD students (B. Marchadier, PE Chazal, R. Mishra, J. Kanaan, V. Busetto, J. Paternina) 5 Post-docs (C. Barrandon, F. Fiorini, Z. Wang, E. Marquenet, O.S. Kwon) 7 Engineers (F. Bonneau, V. Murigneux, L. Bastianelli, R. Servignat d’Aout, R. Hocq, Q.Alasseur, J. Paternina) 1 technician CNRS (I. Barbosa). 9 Master students **COMMUNICATIONS** ================== **Teaching activities** ======================= Since 2009: Master in Genetics, UPMC (3h per year) Since 2009: ENS L3 Chimie (2h per year) Since 2009: ENS Master in Genetics, UPMC (3h per year) 2014: PhD program, Wellcome Trust Centre for Cell Biology, Edinburgh, UK (2014) 2014: PhD program, FMI, Basel, Switzerland (2014) 2012: PhD program, University Toulouse (2012) 2017: Co-organizer and teaching: International course Curie-ENS “Posttranscriptional gene regulation” (2017) **Peer review and expertise activity** ====================================== • Reviewer for several journals including: Cell; Nature; Nature Structural & Molecular Biology; Genes & Development; EMBO Journal; Journal of Cell Biology; Nucleic Acids Research; P.N.A.S.; Cell Report. • Reviewer for several grant agencies including: ERC; Wellcome Trust; ANR; Ligue contre le Cancer; Foreign agencies (Denmark, Poland, Israel, etc…). • Since 2013: Member executive council doctoral school “Complexité du Vivant” – University UPMC (Paris 6). • Since 2015: Member scientifc council “Ligue Grand Est” • 2013-2016: Member scientifc council “Fondation Pierre-Gilles de Gennes” • 2014: Vice-President ANR committee CES10 • 2016: Member ANR committee CES12 • 2017-2020: President ANR committee CES12 **SELECTED PUBLICATIONS** Kanaan Hocq R, Paternina J, Alasseur Q, Genovesio A, **Le Hir H**. (**2018**) Monitored eCLIP: high accuracy mapping of RNA-protein interactions. **Nucleic Acids Research** 2018 Nov;46(21):11553-11565. Kanaan J, Raj S, Decourty L, Saveanu C, Croquette V, **Le Hir H**. (**2018**) UPF1-like helicase grip on nucleic acids dictates processivity. **Nature Communications**. 2018 Sep;14(9):3752. **Le Hir H**, Saulière J, Wang Z. (**2016**) The exon junction complex as a node of postranscriptional networks. **Nature Review in Molecular and Cellular Biology**. 2016 Jan;17(1):41-54. Fiorini F, Bagchi D, **Le Hir H\***, Croquette V\*. (**2015**) Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities. **Nature Communications**. Jul 3;6:7581. \**Corresponding authors* Wang Z, Murigneux V, **Le Hir H**. (**2014**). Transcriptome-wide modulation of splicing by the Exon Junction Complex. **Genome Biology**. 15(12):551. Chazal PE, Daguenet E, Wendling C, Ulrycke N, Tomasetto C, Sargueil B, **Le Hir H** (**2013**). EJC core component MLN51 interacts with eIF3 and activates translation. **P.N.A.S.** 110(15):5903-8. Saulière J, Murigneux V, Wang Z, Marquenet E, Barbosa I, Le Tonquèze O, Audic Y, Paillard L, Roest Crollius H, **Le Hir H**. (**2012**). CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex. **Nature Structural and Molecular Biology** 19(11):1124-31. Barbosa I, Haque N, Fiorini F, Barrandon C, Tomasetto C, Blanchette M, **Le Hir H**. (**2012**). Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. **Nature Structural and Molecular Biology** 19(10):983-90. Chakrabarti S, Jayachandran U, Bonneau F, Fiorini F, Basquin C, Domcke S, Le Hir H, Conti E. (**2011**). Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2. **Molecular Cell** 41(6):682-692. Saulière J, Haque N, Harms S, Barbosa I, Blanchette M, Le Hir H. (**2010**). The exon junction complex differentially marks spliced junctions. **Nature Structural and Molecular Biology** 17(10):1269-71. Le Hir H, Séraphin B. (**2008**). EJCs at the heart of translational control. **Cell**. 133(2):213-6. Chamieh H, Ballut L, Bonneau F, Le Hir H. (**2008**). NMD factors UPF2 and UPF3 bridge UPF1 to the exon junction complex and stimulate its RNA helicase activity. **Nature Structural and Molecular Biology** 15(1):85-93. Andersen CB\*, Ballut L\*, Johansen JS, Chamieh H, Nielsen KH, Oliveira CL, Pedersen JS, Seraphin B, Le Hir H#, Andersen GR#. (**2006**). Structure of the Exon Junction Core Complex with a Trapped DEAD-Box ATPase Bound to RNA. **Science** 313:1968-1972. Ballut L, Marchadier B, Baguet A, Tomasetto C, Séraphin B, Le Hir H. (2005). The Exon-Junction complex is locked onto mRNA by inhibition of eIF4A3 ATPase activity. Nature Structural and Molecular Biology 12(10):861-9. Le Hir, H., Gatfield, D., Izaurralde, E. & Moore, M.J. (**2001**). The exon-exon junction complex provides a binding platform for factors involved in mRNA export and NMD. **The EMBO Journal** 20 (17):4987-4997. Le Hir, H., Izaurralde, E., Maquat, L.E. & Moore, M.J. (**2000**). The spliceosome deposits multiple proteins 20-24 nucleotides upstream of mRNA exon-exon junctions. **The EMBO Journal** 19 (24):6860-6869.

Publications

Image document

Exclusion of m6A from splice-site proximal regions by the exon junction complex dictates m6A topologies and mRNA stability

Anna Uzonyi , David Dierks , Ronit Nir , Oh Sung Kwon , Ursula Toth
Molecular Cell, 2023, 83 (2), pp.237-251.e7. ⟨10.1016/j.molcel.2022.12.026⟩
Article dans une revue hal-04291793v1
Image document

Comprehensive mapping of exon junction complex binding sites reveals universal EJC deposition in Drosophila

Lucía Morillo , Toni Paternina , Quentin Alasseur , Auguste Genovesio , Schraga Schwartz
BMC Biology, 2023, 21 (1), pp.246. ⟨10.1186/s12915-023-01749-1⟩
Article dans une revue hal-04291789v1
Image document

Exon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis

Oh Sung Kwon , Rahul Mishra , Adham Safieddine , Emeline Coleno , Quentin Alasseur
Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-21590-w⟩
Article dans une revue hal-03382897v3
Image document

A role for AKT1 in nonsense-mediated mRNA decay

Martine Palma , Catherine Leroy , Sophie Salomé-Desnoulez , Elisabeth Werkmeister , Rebekah Kong
Nucleic Acids Research, 2021, 49 (19), pp.11022-11037. ⟨10.1093/nar/gkab882⟩
Article dans une revue hal-03423347v1

Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes

Virginia Busetto , Isabelle Barbosa , Jérôme Basquin , Émelie Marquenet , Rémi Hocq
Nucleic Acids Research, 2020, 48 (10), pp.5670-5683. ⟨10.1093/nar/gkaa267⟩
Article dans une revue hal-03419075v1
Image document

Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes

Virginia Busetto , Isabelle Barbosa , Jérôme Basquin , Emélie Marquenet , Rémi Hocq
Nucleic Acids Research, 2020, 48 (10), pp.5670-5683. ⟨10.1093/nar/gkaa267⟩
Article dans une revue pasteur-02862504v1
Image document

A Dual Protein-mRNA Localization Screen Reveals Compartmentalized Translation and Widespread Co-translational RNA Targeting

Racha Chouaib , Adham Safieddine , Xavier Pichon , Arthur Imbert , Oh Sung Kwon
Developmental Cell, 2020, 54 (6), pp.773 - 791.e5. ⟨10.1016/j.devcel.2020.07.010⟩
Article dans une revue pasteur-02925687v1
Image document

NCBP3 positively impacts mRNA biogenesis

Yuhui Dou , Isabelle Barbosa , Hua Jiang , Claudia Iasillo , Kelly Molloy
Nucleic Acids Research, 2020, 48 (18), pp.10413-10427. ⟨10.1093/nar/gkaa744⟩
Article dans une revue hal-03033173v1
Image document

ALFA: annotation landscape for aligned reads

Mathieu Bahin , Benoit Noel , Valentine Murigneux , Charles Bernard , Leila Bastianelli
BMC Genomics, 2019, 20 (250), pp.1-11. ⟨10.1186/s12864-019-5624-2⟩
Article dans une revue hal-02084432v1
Image document

Monitored eCLIP: high accuracy mapping of RNA-protein interactions

Rémi Hocq , Janio Paternina , Quentin Alasseur , Auguste Genovesio , Hervé Le Hir
Nucleic Acids Research, 2018, 46 (21), pp.11553-11565. ⟨10.1093/nar/gky858⟩
Article dans une revue hal-02387433v1
Image document

UPF1-like helicase grip on nucleic acids dictates processivity

Joanne Kanaan , Saurabh Raj , Laurence Decourty , Cosmin Saveanu , Vincent Croquette
Nature Communications, 2018, 9 (1), pp.3752. ⟨10.1038/s41467-018-06313-y⟩
Article dans une revue hal-01878957v1
Image document

Nonsense‐mediated mRNA decay involves two distinct Upf1‐bound complexes

Marine Dehecq , Laurence Decourty , Abdelkader Namane , Caroline Proux , Joanne Kanaan
EMBO Journal, 2018, 37, pp.e99278. ⟨10.15252/embj.201899278⟩
Article dans une revue pasteur-01889054v1
Image document

A conserved structural element in the RNA helicase UPF1 regulates its catalytic activity in an isoform-specific manner

Manjeera Gowravaram , Fabien Bonneau , Joanne Kanaan , Vincent D Maciej , Francesca Fiorini
Nucleic Acids Research, 2018, 46 (5), pp.2648 - 2659. ⟨10.1093/nar/gky040⟩
Article dans une revue hal-01762546v1

HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition

Francesca Fiorini , Jean-Philippe Robin , Joanne Kanaan , Malgorzata Borowiak , Vincent Croquette
Nature Communications, 2018, 9 (1), ⟨10.1038/s41467-017-02793-6⟩
Article dans une revue hal-02358887v1

A mechanistic study of helicases with magnetic traps

Samar Hodeib , Saurabh Raj , Maria Manosas , Weiting Zhang , Debjani Bagchi
Protein Science, 2017, 26 (7), pp.1314-1336. ⟨10.1002/pro.3187⟩
Article dans une revue hal-02358906v1

Human Upf1 is a highly processive RNA helicase and translocase with RNP remodelling activities

Francesca Fiorini , Debjani Bagchi , Hervé Le Hir , Vincent Croquette
Nature Communications, 2015, 6 (1), ⟨10.1038/ncomms8581⟩
Article dans une revue hal-02358918v1

Tight intramolecular regulation of the human Upf1 helicase by its N- and C-terminal domains

Francesca Fiorini , Marc Boudvillain , Hervé Le Hir
Nucleic Acids Research, 2013, 41 (4), pp.2404-2415. ⟨10.1093/nar/gks1320⟩
Article dans une revue hal-02358926v1
Image document

Perispeckles are major assembly sites for the exon junction core complex.

Elisabeth Daguenet , Aurélie Baguet , Sébastien Degot , Ute Schmidt , Fabien Alpy
Molecular Biology of the Cell, 2012, 23 (9), pp.1765-1782. ⟨10.1091/mbc.E12-01-0040⟩
Article dans une revue hal-00727654v1

CLIP-seq of eIF4AIII reveals transcriptome-wide mapping of the human exon junction complex.

Jérôme Saulière , Valentine Murigneux , Zhen Wang , Emélie Marquenet , Isabelle Barbosa
Nature Structural and Molecular Biology, 2012, 19 (11), pp.1124-31. ⟨10.1038/nsmb.2420⟩
Article dans une revue hal-00982626v1

Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly

Isabelle Barbosa , Nazmul Haque , Francesca Fiorini , Charlotte Barrandon , Catherine Tomasetto
Nature Structural and Molecular Biology, 2012, 19 (10), pp.983-990. ⟨10.1038/nsmb.2380⟩
Article dans une revue hal-02358933v1

Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2

Sutapa Chakrabarti , Uma Jayachandran , Fabien Bonneau , Francesca Fiorini , Claire Basquin
Molecular Cell, 2011, 41 (6), pp.693-703. ⟨10.1016/j.molcel.2011.02.010⟩
Article dans une revue hal-02358974v1

Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies.

Karine Buchet-Poyau , Julien Courchet , Hervé Le Hir , Bertrand Séraphin , Jean-Yves Scoazec
Nucleic Acids Research, 2007, 35 (4), pp.1289-300. ⟨10.1093/nar/gkm016⟩
Article dans une revue hal-00167447v1
Image document

The exon-junction-complex-component metastatic lymph node 51 functions in stress-granule assembly.

Aurélie Baguet , Sébastien Degot , Nicolas Cougot , Edouard Bertrand , Marie-Pierre Chenard
Journal of Cell Science, 2007, 120 (Pt 16), pp.2774-84. ⟨10.1242/jcs.009225⟩
Article dans une revue hal-00189164v1

Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA.

Christian B F Andersen , Lionel Ballut , Jesper S Johansen , Hala Chamieh , Klaus H Nielsen
Science, 2006, 313 (5795), pp.1968-72. ⟨10.1126/science.1131981⟩
Article dans une revue hal-00168014v1

The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity.

Lionel Ballut , Brice Marchadier , Aurélie Baguet , Catherine Tomasetto , Bertrand Séraphin
Nature Structural and Molecular Biology, 2005, 12 (10), pp.861-9. ⟨10.1038/nsmb990⟩
Article dans une revue hal-00187421v1