RNA polymerase III | Labo-teichmann

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Ferrari-TFIIIC-paper-2022

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Ferrari-TFIIIC-paper-2022

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Targeting Transcription in Breast Cancer (TTBC)

Lab Members

Angélique Alonso-Marrau
Technician
email: Angelique.Alonso-Marrau@u-bordeaux.fr
phone: ++33-5-5757-9504

Monica Arnedos
Practicien Hospitalier
email: m.arnedos@bordeaux.unicancer.fr
phone: ++33-

Hervé Bonnefoi
Professor Practicien Hospitalier
email: H.Bonnefoi@bordeaux.unicancer.fr
phone: ++33-

Elodie Darbo
Research Engineer
email: elodie.darbo@u-bordeaux.fr
phone: ++33-

Richard Iggo
Professor
email: r.iggo@bordeaux.unicancer.fr
phone: ++33-

Elisabeth Lata
PhD student
email: Elisabeth.Lata@etu.u-bordeaux.fr
phone: ++33-5-5757-9504

Gaëtan McGrogan
Practicien Hospitalier
email: G.MacGrogan@bordeaux.unicancer.fr
phone: ++33-

Anne Persoz
Research Engineer
email: anne.persoz@inserm.fr
phone: ++33-

Francis Sagliocco
Associate Professor
Coordinator of the Master of Cellular and Molecular Genetics
email: Francis.Sagliocco@u-bordeaux.fr
phone: ++33-5-5757-9504

Martin Teichmann
Professor
Director of the Doctoral School of
Life Sciences and Health
email: Martin.Teichmann@inserm.fr
phone: ++33-5-5757-4647

Research

Our goal is to understand the role of transcription factors acting at specific steps in the mammary lineage and to develop treatments based on targeting transcription in breast cancer cells. We classified breast cancer into three major groups (luminal, molecular apocrine and basal, Farmer et al., 2005), and recently developed an algorithm based on transcription factor expression to classify tumours into these groups (Iggo, 2018).

To target luminal tumours that are resistant to existing anti-estrogen therapies we are developing strategies based on selective androgen receptor modulators (SARMs, Hickey et al., 2020).

To target molecular apocrine tumours, we have performed two clinical trials with anti-androgens (NCT01842321 and NCT03383679) but we need to better understand the biology of these tumours.

To target basal and stem cell-like tumours (commonly referred to as TNBC in the clinical literature because they do not express the estrogen receptor ER, the progesterone receptor [PR] or ERBB2 [HER2]), we are exploring an embryonic isoform of RNA polymerase III as a potential target.

Recherche

Notre objectif est de comprendre le rôle des facteurs de transcription agissant à des étapes spécifiques de la lignée mammaire et de développer des traitements basés sur le ciblage de la transcription dans les cellules du cancer du sein. Nous avons classé le cancer du sein en trois grands groupes (luminal, apocrine moléculaire et basal, Farmer et al., 2005), et avons récemment développé un algorithme basé sur l'expression des facteurs de transcription pour classer les tumeurs dans ces groupes (Iggo, 2018).

Pour cibler les tumeurs luminales qui sont résistantes aux thérapies anti-œstrogènes existantes, nous développons des stratégies basées sur les modulateurs sélectifs des récepteurs aux androgènes (SARMs, Hickey et al., 2020).

Pour cibler les tumeurs apocrines moléculaires, nous avons réalisé deux essais cliniques avec des anti-androgènes (NCT01842321 et NCT03383679) mais nous devons mieux comprendre la biologie de ces tumeurs.

Pour cibler les tumeurs basales et les tumeurs semblables aux cellules souches (communément appelées TNBC dans la littérature clinique car elles n'expriment pas le recepteur d'éstrogène [ER], le récepteur de la progestérone [PR] ou ERBB2 [HER2]), nous explorons une isoforme embryonnaire de l'ARN polymérase III comme cible potentielle.

News

February, 2022: Our new article is out in "International Journal of Molecular Sciences"

An RNA Polymerase III General Transcription Factor Engages in Cell Type-Specific Chromatin Looping. de Llobet Cucalon L, Di Vona C, Morselli M, Vezzoli M, Montanini B, Teichmann M, de la Luna S, Ferrari R. Int J Mol Sci. 2022 Feb 18;23(4):2260. doi: 10.3390/ijms23042260.

Teaching

Our Team members are participating in teaching modules of the bachelor degree and of the Masters of Genetics (GMC), Cellular Biology (BCPP), Cancer Biology and Biochemistry of the University of Bordeaux.

For more detailed information, please contact the laboratory.

Enseignement

Les membres de notre équipe participent aux modules d’enseignement de la Licence et des Master de l’Université de Bordeaux en génétique (GMC), en biologie cellulaire (BCPP), en biologie du cancer et en biochimie.

Pour plus d'informations, veuillez contacter le laboratoire.

Selected Publications

An RNA Polymerase III General Transcription Factor Engages in Cell Type-Specific Chromatin Looping.
de Llobet Cucalon L, Di Vona C, Morselli M, Vezzoli M, Montanini B, Teichmann M, de la Luna S, Ferrari R. Int J Mol Sci. 2022 Feb 18;23(4):2260. doi: 10.3390/ijms23042260.

RNA Polymerase III Subunit Mutations in Genetic Diseases.

Lata E, Choquet K, Sagliocco F, Brais B, Bernard G, Teichmann M. Front Mol Biosci. 2021 Jul 30;8:696438. doi: 10.3389/fmolb.2021.696438. eCollection 2021.

Activation and repression at the heart of human RNA polymerase III.

Lata E, Teichmann M. Nat Struct Mol Biol. 2021 Feb;28(2):124-126. doi: 10.1038/s41594-021-00561-1.

TFIIIC Binding to Alu Elements Controls Gene Expression via Chromatin Looping and Histone Acetylation.

Ferrari R, de Llobet Cucalon LI, Di Vona C, Le Dilly F, Vidal E, Lioutas A, Oliete JQ, Jochem L, Cutts E, Dieci G, Vannini A, Teichmann M, de la Luna S, Beato M. Mol Cell. 2020 Feb 6;77(3):475-487.e11. doi: 10.1016/j.molcel.2019.10.020.

The hRPC62 subunit of human RNA polymerase III displays helicase activity.

El Ayoubi L, Dumay-Odelot H, Chernev A, Boissier F, Minvielle-Sébastia L, Urlaub H, Fribourg S, Teichmann M.

Nucleic Acids Res. 2019 Sep 16. pii: gkz788. doi: 10.1093/nar/gkz788.

https://academic.oup.com/nar/advance-article/doi/10.1093/nar/gkz788/5569986?searchresult=1

Fusion-mediated genomic instability promotes aneuploidy patterns that resemble human tumors.

Delespaul, L, Merle , C, Lesluyes, T, Lagarde, P, Le Guellec, S, Pérot, G, Baud, J, Prochazkova-Carlotti, M, Danet, C, Fèvre, M, Rousseau, B, Durrieu-Gaillard, S, Teichmann, M, Coindre, JM, Lartigue, L, Chibon, F. Oncogene. 2019 Jul 3. doi: 10.1038/s41388-019-0859-6. [Epub ahead of print]

https://www.nature.com/articles/s41388-019-0859-6

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200.

Karine Choquet, K, Forget, D, Meloche, E, Dicaire, MJ, Bernard, G, Vanderver, A, Schiffmann, R, Fabian, M, Teichmann, M, Coulombe, B, Brais, B, and Kleinman, C. J Biol Chem. 2019 May 3;294(18):7445-7459. doi: 10.1074/jbc.RA118.006271.

http://www.jbc.org/content/early/2019/03/21/jbc.RA118.006271

CRISPR/Cas9 genome editing induces megabase-scale chromosomal truncations.

Cullot, G, Boutin, J, Toutain, J, Prat, F, Pennamen, P, Rooryck, C, Teichmann, M, Rousseau, E, Lamrissi-Garcia, I, Guyonnet-Duperat, V, Bibeyran, A, Lalanne, M, Prouzet-Mauléon, V, Turcq, B, Ged, C, Blouin, JM, Richard, E, Dabernat, S, Moreau-Gaudry, F, Bedel, A.

Nat Commun. 2019 Mar 8;10(1):1136. doi: 10.1038/s41467-019-09006-2.

https://doi.org/10.1038/s41467-019-09006-2

Effects on prostate cancer cells of targeting RNA polymerase III.
Petrie1, JL, Swan, C, Ingram, RM, Frame, FM, Collins, AT, Dumay-Odelot, H, Teichmann, M, Maitland, NJ, White, RJ.

Nucleic Acids Res. 2019 May 7;47(8):3937-3956. doi: 10.1093/nar/gkz128.

https://doi.org/10.1093/nar/gkz128

Mutation in POLR3K causes hypomyelinating leukodystrophy and abnormal ribosomal RNA regulation.

Dorboz I, Dumay-Odelot H, Boussaid K, Bouyacoub Y, Barreau P, Samaan S, Jmel H, Eymard-Pierre E, Cances C, Bar C, Poulat AL, Rousselle C, Renaldo F, Elmaleh-Bergès M, Teichmann M, Boespflug-Tanguy O.

Neurol Genet. 2018 Dec 3;4(6):e289.

https://doi.org/10.1212/NXG.0000000000000289

Regulation of RNA polymerase III transcription during transformation of human IMR90 fibroblasts with defined genetic elements.

Durrieu-Gaillard S, Dumay-Odelot H, Boldina G, Tourasse NJ, Allard D, André F, Macari F, Choquet A, Lagarde P, Drutel G, Leste-Lasserre T, Petitet M, Lesluyes T, Lartigue-Faustin L, Dupuy JW, Chibon F, Roeder RG, Joubert D, Vagner S, Teichmann M.

Cell Cycle. 2018;17(5):605-615.

https://doi.org/10.1080/15384101.2017.1405881

Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation.

Choquet K, Yang S, Moir RD, Forget D, Larivière R, Bouchard A, Poitras C, Sgarioto N, Dicaire MJ, Noohi F, Kennedy TE, Rochford J, Bernard G, Teichmann M, Coulombe B, Willis IM, Kleinman CL, Brais B.

Mol Brain. 2017 Apr 13;10(1):13.

https://doi.org/10.1186/s13041-017-0294-y

TRM6/61 connects PKCα with translational control through tRNAi(Met) stabilization: impact on tumorigenesis.

Macari F, El-Houfi Y, Boldina G, Xu H, Khoury-Hanna S, Ollier J, Yazdani L, Zheng G, Bièche I, Legrand N, Paulet D, Durrieu S, Byström A, Delbecq S, Lapeyre B, Bauchet L, Pannequin J, Hollande F, Pan T, Teichmann M, Vagner S, David A, Choquet A, Joubert D.

Oncogene. 2016 Apr 7;35(14):1785-96.

https://doi.org/10.1038/onc.2015.244

Structural analysis of human RPC32β-RPC62 complex.

Boissier F, Dumay-Odelot H, Teichmann M, Fribourg S.

J Struct Biol. 2015 Dec;192(3):313-319.

https://doi.org/10.1016/j.jsb.2015.09.004

Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles.

Walz S, Lorenzin F, Morton J, Wiese KE, von Eyss B, Herold S, Rycak L, Dumay-Odelot H, Karim S, Bartkuhn M, Roels F, Wüstefeld T, Fischer M, Teichmann M, Zender L, Wei CL, Sansom O, Wolf E, Eilers M.

Nature. 2014 Jul 24;511(7510):483-7.

https://doi.org/10.1038/nature13473

Contributions of in vitro transcription to the understanding of human RNA polymerase III transcription.

Dumay-Odelot H, Durrieu-Gaillard S, El Ayoubi L, Parrot C, Teichmann M.

Transcription. 2014;5(1):e27526.

https://doi.org/10.4161/trns.27526

RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

Pascali C, Teichmann M.

Subcell Biochem. 2013;61:261-87.

https://doi.org/10.1007/978-94-007-4525-4_12

Recessive mutations in POLR3B, encoding the second largest subunit of Pol III, cause a rare hypomyelinating leukodystrophy.

Tétreault M, Choquet K, Orcesi S, Tonduti D, Balottin U, Teichmann M, Fribourg S, Schiffmann R, Brais B, Vanderver A, Bernard G.

Am J Hum Genet. 2011 Nov 11;89(5):652-5.

https://doi.org/10.1016/j.ajhg.2011.10.006

Mutations of POLR3A encoding a catalytic subunit of RNA polymerase Pol III cause a recessive hypomyelinating leukodystrophy.

Bernard G, Chouery E, Putorti ML, Tétreault M, Takanohashi A, Carosso G, Clément I, Boespflug-Tanguy O, Rodriguez D, Delague V, Abou Ghoch J, Jalkh N, Dorboz I, Fribourg S, Teichmann M, Megarbane A, Schiffmann R, Vanderver A, Brais B.

Am J Hum Genet. 2011 Sep 9;89(3):415-23.

https://doi.org/10.1016/j.ajhg.2011.07.014

Widespread occurrence of non-canonical transcription termination by human RNA polymerase III.

Orioli A, Pascali C, Quartararo J, Diebel KW, Praz V, Romascano D, Percudani R, van Dyk LF, Hernandez N, Teichmann M, Dieci G.

Nucleic Acids Res. 2011 Jul;39(13):5499-512.

https://doi.org/10.1093/nar/gkr074

Structure-function analysis of hRPC62 provides insights into RNA polymerase III transcription initiation.

Lefèvre S, Dumay-Odelot H, El-Ayoubi L, Budd A, Legrand P, Pinaud N, Teichmann M, Fribourg S.

Nat Struct Mol Biol. 2011 Mar;18(3):352-8.

https://doi.org/10.1038/nsmb.1996

General transcription factors and subunits of RNA polymerase III: Paralogs for promoter- and cell type-specific transcription in multicellular eukaryotes.

Teichmann M, Dieci G, Pascali C, Boldina G.