Parent Category: Laboratoires Published: Monday, 05 March 2012

RNA Biogenesis

 

Bertrand

 Edouard BERTRAND

 

 IGMM - UMR 5535

 1919, route de Mende, 34293 Montpellier

 

Phone: +33 4 34 35 96 47

Email : edouard.bertrand@igmm.cnrs.fr

 

 Website

 

 

Our goals is to provide a better understanding of gene expression at the cellular level, with two lines of research:

1)-Imaging transcription and RNA processing in live cells.

RNA biogenesis is subject to many regulatory events, and defining the kinetic parameters of transcription and RNA processing becomes key to understand gene regulation. Over the past decade, we have developed fluorescent microscopy approaches to visualize single mRNPs in living cells (Fusco, 2003; Basyuk, 2003), and to quantitatively measure transcription and mRNA processing, including splicing (Boireau, 2007; Munoz, 2009; Schmidt, 2011). Our aim is to measure the activity of single molecules of RNA polymerase II on single copy genes in real-time. This will provide a detailled view of transcription initiation, elongation and RNA 3'-end processing, and will provide new mechanistic information on this fundamental step of gene expression.

2)-Understanding assembly of RNP particles.

Many non-coding RNA function as stable RNP particles. This requires dedicated machineries to assemble these RNPs and transport them to their site of function. We study these questions using snoRNPs as a model system. We discovered two key complexes, R2TP and CBCAP.

The R2TP is an HSP90 co-chaperone that assembles snoRNP and the three RNA polymerases, and thus the basic machineries of gene expression (Boulon, 2007, 2010). The R2TP appears to be a machinery specialized in the assembly of target complexes. Our aim is to characterize its mechanism of action and all its client complexes.

The CBCAP complex binds thousands of capped and abundant RNAs, and physically links the two ends of nascent RNA molecules by linking the cap to 3'-end processing machineries (Boulon 2004; Hallais, unpublished). Our aim is to characterize its cellular and molecular functions.

The R2TP and CBCAP complexes open new routes to understand RNA biogenesis and its link to cell growth and cancer.

 

Keywords: RNA processing, transcription, RNA trafficking, RNP assembly, live cell imaging

 

 

Main publications

 

  • Assembly of the U5 snRNP component PRPF8 is controlled by the HSP90/R2TP chaperones. J. Cell Biol., in press. Malinová, A., Cvačková, Z., Matějů, D., Hořejší, Z., Abéza, C., Vandermoere, F., Bertrand, E.*, Staněk, D.*, Verheggen, C.*    *. co-corresponding authors.
  • Mutually exclusive CBC-containing complexes contribute to RNA fate. Cell Reports, 2017, 18:2635-2650. Giacometti, S., Benbahouche, N. H., Domanski, M., Robert, M-C., Meola, N., Lubas, M., Bukenborg, J., Andersen, J. S., Schultze, W. M., Verheggen, C., Kudla, G.*, Jensen, T. H.*, Bertrand, E.*      *:co-corresponding authors
  • SmiFISH and FISH-quant -  a flexible single mRNA detection approach with super-resolution capability. Nucleic Acids Res, 2016, pii:gwk784, Tsanov, N., Samacoits, A., Chouaib, R., Traboulsi, A.M., Gostan, T., Weber, C., Zimmer, C., Zibara, K., Walter, T., Peter, M.*, Bertrand, E.*, Mueller, F*        *. co-corresponding authors.
  • Visualization of single polysomes reveals translation dynamics of endogenous mRNAs in living human cells, J. Cell Biol., 2016, 214:769-81. Pichon X., Bastide A., Safieddine A., Chouaib R., Samacoits A., Basyuk E., Peter M., Mueller F., Bertrand E.      Spotlight article, see commentary in doi:10.1083/jcb.201608075, selected by F1000
  • A Real time, single molecule view of transcription reveals convoys of RNA polymerases and multiscale bursting. Nat. Comm., 2016, 7:12248. Tantale, K., Müller, F., Kozulic-Pirher, A., Lesne, A., Victor, JL., Robert, MC., Capozi, S., Bäcker, V., Mateos-Langerak, J., Darzacq, X., Zimmer, C., Basyuk, E., Bertrand, E.    Selected by F1000
  • NUFIP and the HSP90/R2TP chaperone bind the SMN complex and facilitate assembly of U4-specific proteins. Nucl Acids Res, 2015, 43:8973-87. Bizarro, J., Dodré, M., Huttin, A., Charpentier, B., Schlotter, F., Branlant, C., Verheggen, C., Massenet, S., Bertrand, E.
  • Proteomic and 3D structure analyses highlight the C/D box snoRNP assembly mechanism and its control. J. Cell Biol., 2014; 207:463-480. Bizarro, J., Charron, C., Boulon, S., Westman, B., Pradet-Balade, B., Vandermoere, F., Chagot, ME., Hallais, M., Ahmad, Y., Leonhardt, H., Lamond, A., Manival, X., Branlant, C., Charpentier, B., Verheggen*, C., Bertrand*, E.            *: co-corresponding authors.
  • Characterization of spaghetti function in Drosophila supports a role for Hsp70 in R2TP/Hsp90-assisted assembly of cellular machineries. J Biol Chem, 2014, 289(9):6236-47. Benbahouche, H., Iliopoulos, I., Török, I., Marhold, J., Kajava, A., Kempf, T., Schnölzer, M., Kiss, I., Bertrand, E.*, Mechler*, B. M.*, Pradet-Balade, B.*               *: co-corresponding authors.               Selected best paper of 2014 by JBC editors (among 20 other papers)
  • Stable assembly of HIV-1 export complexes occurs co-transcriptionally. RNA, 2014, 20:1-8. Nawroth, I., Mueller, F., Basyuk, E., Beerens, N., Rahbek, U. Darzacq, X., Bertrand, E.*, Kjems, J.* and Schmidt, U.*                *: co-corresponding authors.
  • Identification of the interface between Snu13p/15.5K and Rsa1p/NUFIP and demonstration of its functional importance for snoRNP assembly. Nucl Acids Res, 2014, 42(3):2015-36. Rothé, B., Back, R., Quinternet, M., Bizarro, J., Robert, M-C., Blaud, M., Romier, C., Manival, X.*, Charpentier, B.*, Bertrand, E.*, Branlant, C.               *: co-corresponding authors. 
  • CBC-ARS2 stimulate 3'-end maturation of multiple RNA families and favor cap-proximal processing. Nat Struc Mol Biol, 2013, 20:1367-76. Hallais, M., Pontvianne, F., Refsing Andersen, P., Clerici, M., Lener, D., Benbahouche, H., Gostan, T.,Vandermoere, F., Robert, M-C., Cusack, S., Verheggen, C., Jensen, T. H. and Bertrand, E.               Highlited in NSMB and Nature Reviews
  • The human cap-binding complex is functionally connected to the nuclear RNA exosome. Nat Struc Mol Biol, 2013, 20:1358-66. Refsing Andersen, P., Domanski, M., Kristiansen, M., Storvall, E., Ntini, E., Verheggen, C., Bunkenborg, J., Poser, I., Hallais, M., Sandberg, R., Hyman, A., LaCava, J., Rout, M. P., Andersen, J. S., Bertrand, E., and Jensen, T. H.               Highlited in NSMB and Nature Reviews
  • Fish-quant : automated counting of transcripts in 3D images. Nat Methods. 2013, 10:277-8. Mueller F, Senecal A, Tantale K, Marie-Nelly H, Ly N, Collin O, Basyuk E, Bertrand E*, Darzacq X*, Zimmer C*.                       * : co-corresponding authors.
  • Nuclear retention prevents premature cytoplasmic appearance of mRNA. Mol Cell, 2012, 48:145-152. Kallehauge,T., Robert, M-C., Bertrand*, E., Jensen*, T. H.                 *: co-corresponding authors.
  • HSP90 and the R2TP co-chaperone complex: building multi-protein machineries essential for cell growth and gene expression. RNA Biol, 2012, 9: 148-54. Boulon, S., Bertrand, E.*, and B. Pradet-Balade*.               *: co-corresponding authors
  • CRM1 plays a nuclear role in transporting snoRNPs to nucleoli in higher eukaryotes. Nucleus. 2012. 3(2). Verheggen C, Bertrand E.
  • CRM1 controls the composition of nucleoplasmic pre-snoRNA complexes to licence them for nucleolar transport. EMBO J., 2011, 30:2205-2218. Pradet-Balade, B., Girard, C., Boulon, S., Paul, C., Azzag, K., Bordonne, R., Bertrand, E.*, and Verheggen, C*         *: co-corresponding authors.
  • Real-time imaging of co-transcriptional splicing reveals a kinetic model that reduces noise: implication for alternative splicing regulation. J Cell Biol, 2011, 193:819-829.Schmidt, U., Basyuk, E., Robert, MC., Yoshida, M., Villemin, JP., Auboeuf, D., Aitken, S. and Bertrand, E.           Highlited in J Cell Biol Biobytes.

 

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