Hervé LE HIR

30
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 : Prime d’Encadrement Doctoral et de Recherche 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

Publications

Image document

RNA anchoring of Upf1 facilitates recruitment of Dcp2 in the NMD decapping complex

Nadia Ruiz-Gutierrez , Jeanne Dupas , Elvire Auquier , Irène Barbarin-Bocahu , Claudine Gaudon-Plesse et al.
Nucleic Acids Research, 2025, 53 (5), pp.gkaf160. ⟨10.1093/nar/gkaf160⟩
Article dans une revue hal-05051133 v1
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Exon-junction complex association with stalled ribosomes and slow translation-independent disassembly

Olivier Bensaude , Isabelle Barbosa , Lucia Morillo , Rivka Dikstein , Hervé Le Hir
Nature Communications, 2024, 15 (1), pp.4209. ⟨10.1038/s41467-024-48371-5⟩
Article dans une revue hal-04758965 v1
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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 et al.
Molecular Cell, 2023, 83 (2), pp.237-251.e7. ⟨10.1016/j.molcel.2022.12.026⟩
Article dans une revue hal-04291793 v1
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Comprehensive mapping of exon junction complex binding sites reveals universal EJC deposition in Drosophila

Lucía Morillo , Toni Paternina , Quentin Alasseur , Auguste Genovesio , Schraga Schwartz et al.
BMC Biology, 2023, 21 (1), pp.246. ⟨10.1186/s12915-023-01749-1⟩
Article dans une revue hal-04291789 v1
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Exon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis

Oh Sung Kwon , Rahul Mishra , Adham Safieddine , Emeline Coleno , Quentin Alasseur et al.
Nature Communications, 2021, 12 (1), ⟨10.1038/s41467-021-21590-w⟩
Article dans une revue hal-03382897 v3
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A role for AKT1 in nonsense-mediated mRNA decay

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

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 et al.
Nucleic Acids Research, 2020, 48 (10), pp.5670-5683. ⟨10.1093/nar/gkaa267⟩
Article dans une revue hal-03419075 v1
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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 et al.
Developmental Cell, 2020, 54 (6), pp.773 - 791.e5. ⟨10.1016/j.devcel.2020.07.010⟩
Article dans une revue pasteur-02925687 v1
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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 et al.
Nucleic Acids Research, 2020, 48 (10), pp.5670-5683. ⟨10.1093/nar/gkaa267⟩
Article dans une revue pasteur-02862504 v1
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NCBP3 positively impacts mRNA biogenesis

Yuhui Dou , Isabelle Barbosa , Hua Jiang , Claudia Iasillo , Kelly Molloy et al.
Nucleic Acids Research, 2020, 48 (18), pp.10413-10427. ⟨10.1093/nar/gkaa744⟩
Article dans une revue hal-03033173 v1
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ALFA: annotation landscape for aligned reads

Mathieu Bahin , Benoit Noel , Valentine Murigneux , Charles Bernard , Leila Bastianelli et al.
BMC Genomics, 2019, 20 (250), pp.1-11. ⟨10.1186/s12864-019-5624-2⟩
Article dans une revue hal-02084432 v1
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Nonsense‐mediated mRNA decay involves two distinct Upf1‐bound complexes

Marine Dehecq , Laurence Decourty , Abdelkader Namane , Caroline Proux , Joanne Kanaan et al.
EMBO Journal, 2018, 37, pp.e99278. ⟨10.15252/embj.201899278⟩
Article dans une revue pasteur-01889054 v1
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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 et al.
Nature Communications, 2018, 9 (1), ⟨10.1038/s41467-017-02793-6⟩
Article dans une revue hal-02358887 v1
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-02387433 v1
Image document

UPF1-like helicase grip on nucleic acids dictates processivity

Joanne Kanaan , Saurabh Raj , Laurence Decourty , Cosmin Saveanu , Vincent Croquette et al.
Nature Communications, 2018, 9 (1), pp.3752. ⟨10.1038/s41467-018-06313-y⟩
Article dans une revue hal-01878957 v1
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 et al.
Nucleic Acids Research, 2018, 46 (5), pp.2648 - 2659. ⟨10.1093/nar/gky040⟩
Article dans une revue hal-01762546 v1

A mechanistic study of helicases with magnetic traps

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

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), pp.7581. ⟨10.1038/ncomms8581⟩
Article dans une revue hal-02358918 v1

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-02358926 v1

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

Jérôme Saulière , Valentine Murigneux , Zhen Wang , Emélie Marquenet , Isabelle Barbosa et al.
Nature Structural and Molecular Biology, 2012, 19 (11), pp.1124-31. ⟨10.1038/nsmb.2420⟩
Article dans une revue istex hal-00982626 v1
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Perispeckles are major assembly sites for the exon junction core complex.

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

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

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

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 et al.
Molecular Cell, 2011, 41 (6), pp.693-703. ⟨10.1016/j.molcel.2011.02.010⟩
Article dans une revue hal-02358974 v1

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 et al.
Nucleic Acids Research, 2007, 35 (4), pp.1289-300. ⟨10.1093/nar/gkm016⟩
Article dans une revue hal-00167447 v1
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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 et al.
Journal of Cell Science, 2007, 120 (Pt 16), pp.2774-84. ⟨10.1242/jcs.009225⟩
Article dans une revue hal-00189164 v1

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 et al.
Science, 2006, 313 (5795), pp.1968-72. ⟨10.1126/science.1131981⟩
Article dans une revue hal-00168014 v1

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 et al.
Nature Structural and Molecular Biology, 2005, 12 (10), pp.861-9. ⟨10.1038/nsmb990⟩
Article dans une revue istex hal-00187421 v1