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Accueil > Départements > Biologie des Génomes > Marc MIRANDE : Assemblages supramoléculaires et traduction

Publications

2018


  • M. Comisso, A. Hadchouel, J. de Blic, et M. Mirande, « Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity », The FEBS journal, mai 2018.
    Résumé : Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in MARS-related PAP are currently unknown. In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNAMet -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP.
    Mots-clés : aminoacylation kinetics, BDG, MARS, methionyl-tRNA synthetase, pulmonary alveolar proteinosis.

  • F. Khoder-Agha, J. M. Dias, M. Comisso, et M. Mirande, « Characterization of association of human mitochondrial lysyl-tRNA synthetase with HIV-1 Pol and tRNA3Lys », BMC biochemistry, vol. 19, nᵒ 1, p. 2, mars 2018.
    Résumé : BACKGROUND: An important step in human immunodeficiency virus type 1 (HIV-1) replication is the packaging of tRNA3Lysfrom the host cell, which plays the role of primer RNA in the process of initiation of reverse transcription. The viral GagPol polyprotein precursor, and the human mitochondrial lysyl-tRNA synthetase (mLysRS) from the host cell, have been proposed to be involved in the packaging process. More specifically, the catalytic domain of mLysRS is supposed to interact with the transframe (TF or p6*) and integrase (IN) domains of the Pol region of the GagPol polyprotein. RESULTS: In this work, we report a quantitative characterization of the protein:protein interactions between mLysRS and its viral partners, the Pol polyprotein, and the isolated integrase and transframe domains of Pol. A dissociation constant of 1.3 ± 0.2 nM was determined for the Pol:mLysRS interaction, which exemplifies the robustness of this association. The protease and reverse transcriptase domains of GagPol are dispensable in this association, but the TF and IN domains have to be connected by a linker polypeptide to recapitulate a high affinity partner for mLysRS. The binding of the viral proteins to mLysRS does not dramatically enhance the binding affinity of mLysRS for tRNA3Lys. CONCLUSIONS: These data support the conclusion that the complex formed between GagPol, mLysRS and tRNA3Lys, which involves direct interactions between the IN and TF domains of Pol with mLysRS, is more robust than suggested by the previous models supposed to be involved in the packaging of tRNA3Lysinto HIV-1 particles.
    Mots-clés : BDG, Binding affinity, HIV-1, Integrase, MARS, Mitochondrial lysyl-tRNA synthetase, Transframe (TF or p6*), tRNA3 Lys packaging.

  • B. Negrutskii, D. Vlasenko, M. Mirande, P. Futernyk, et A. El'skaya, « mRNA-Independent way to regulate translation elongation rate in eukaryotic cells », IUBMB life, févr. 2018.
    Résumé : The question of what governs the translation elongation rate in eukaryotes has not yet been completely answered. Earlier, different availability of different tRNAs was considered as a main factor involved, however, recent data revealed that the elongation rate does not always depend on tRNA availability. Here, we offer another, codon-independent approach to explain specific tRNA-dependence of the elongation rate in eukaryotes. We hypothesize that the exit rate of eukaryotic translation elongation factor 1A (eEF1A)*GDP from the 80S ribosome depends on the protein affinity to specific aminoacyl-tRNA remaining on the ribosome after GTP hydrolysis. Subsequently, a slower dissociation of eEF1A*GDP from certain aminoacyl-tRNAs in the ribosome can negatively influence the ribosomal elongation rate in a tRNA-dependent and mRNA-independent way. The specific tRNA-dependent departure rate of eEF1A*GDP from the ribosome is suggested to be a novel factor contributing to the overall translation elongation control in eukaryotic cells. © 2018 IUBMB Life, 2018.
    Mots-clés : BDG, DBG, eukaryotic gene expression, MARS, protein synthesis, Ribosome.

2017


  • M. Mirande, « The Aminoacyl-tRNA Synthetase Complex », Sub-Cellular Biochemistry, vol. 83, p. 505-522, 2017.
    Résumé : Aminoacyl-tRNA synthetases (AARSs) are essential enzymes that specifically aminoacylate one tRNA molecule by the cognate amino acid. They are a family of twenty enzymes, one for each amino acid. By coupling an amino acid to a specific RNA triplet, the anticodon, they are responsible for interpretation of the genetic code. In addition to this translational, canonical role, several aminoacyl-tRNA synthetases also fulfill nontranslational, moonlighting functions. In mammals, nine synthetases, those specific for amino acids Arg, Asp, Gln, Glu, Ile, Leu, Lys, Met and Pro, associate into a multi-aminoacyl-tRNA synthetase complex, an association which is believed to play a key role in the cellular organization of translation, but also in the regulation of the translational and nontranslational functions of these enzymes. Because the balance between their alternative functions rests on the assembly and disassembly of this supramolecular entity, it is essential to get precise insight into the structural organization of this complex. The high-resolution 3D-structure of the native particle, with a molecular weight of about 1.5 MDa, is not yet known. Low-resolution structures of the multi-aminoacyl-tRNA synthetase complex, as determined by cryo-EM or SAXS, have been reported. High-resolution data have been reported for individual enzymes of the complex, or for small subcomplexes. This review aims to present a critical view of our present knowledge of the aminoacyl-tRNA synthetase complex in 3D. These preliminary data shed some light on the mechanisms responsible for the balance between the translational and nontranslational functions of some of its components.
    Mots-clés : Aminoacyl-tRNA synthetase (AARS), Core synthetases, Crystal Structure, DBG, MARS, MSC assembly, Multi-aminacyl-tRNA synthetase complex (MSC).

2016



  • L. Kobbi, J. Dias, M. Comisso, et M. Mirande, « Association of human mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol does not require other viral proteins », Biochimie Open, vol. 2, p. 52-61, 2016.

  • A. Rémion, F. Khoder-Agha, D. Cornu, M. Argentini, V. Redeker, et M. Mirande, « Identification of protein interfaces within the multi-aminoacyl-tRNA synthetase complex: the case of lysyl-tRNA synthetase and the scaffold protein p38 », FEBS open bio, vol. 6, nᵒ 7, p. 696-706, juill. 2016.
    Résumé : Human cytoplasmic lysyl-tRNA synthetase (LysRS) is associated within a multi-aminoacyl-tRNA synthetase complex (MSC). Within this complex, the p38 component is the scaffold protein that binds the catalytic domain of LysRS via its N-terminal region. In addition to its translational function when associated to the MSC, LysRS is also recruited in nontranslational roles after dissociation from the MSC. The balance between its MSC-associated and MSC-dissociated states is essential to regulate the functions of LysRS in cellular homeostasis. With the aim of understanding the rules that govern association of LysRS in the MSC, we analyzed the protein interfaces between LysRS and the full-length version of p38, the scaffold protein of the MSC. In a previous study, the cocrystal structure of LysRS with a N-terminal peptide of p38 was reported [Ofir-Birin Y et al. (2013) Mol Cell 49, 30-42]. In order to identify amino acid residues involved in interaction of the two proteins, the non-natural, photo-cross-linkable amino acid p-benzoyl-l-phenylalanine (Bpa) was incorporated at 27 discrete positions within the catalytic domain of LysRS. Among the 27 distinct LysRS mutants, only those with Bpa inserted in place of Lys356 or His364 were cross-linked with p38. Using mass spectrometry, we unambiguously identified the protein interface of the cross-linked complex and showed that Lys356 and His364 of LysRS interact with the peptide from Pro8 to Arg26 in native p38, in agreement with the published cocrystal structure. This interface, which in LysRS is located on the opposite side of the dimer to the site of interaction with its tRNA substrate, defines the core region of the MSC. The residues identified herein in human LysRS are not conserved in yeast LysRS, an enzyme that does not associate within the MSC, and contrast with the residues proposed to be essential for LysRS:p38 association in the earlier work.
    Mots-clés : cross‐link, DBG, lysyl‐tRNA synthetase, MARS, multisynthetase complex, p38, PF, protein:protein interaction, SICAPS.

2015


  • S. Havrylenko et M. Mirande, « Aminoacyl-tRNA synthetase complexes in evolution », International Journal of Molecular Sciences, vol. 16, nᵒ 3, p. 6571-6594, mars 2015.
    Résumé : Aminoacyl-tRNA synthetases are essential enzymes for interpreting the genetic code. They are responsible for the proper pairing of codons on mRNA with amino acids. In addition to this canonical, translational function, they are also involved in the control of many cellular pathways essential for the maintenance of cellular homeostasis. Association of several of these enzymes within supramolecular assemblies is a key feature of organization of the translation apparatus in eukaryotes. It could be a means to control their oscillation between translational functions, when associated within a multi-aminoacyl-tRNA synthetase complex (MARS), and nontranslational functions, after dissociation from the MARS and association with other partners. In this review, we summarize the composition of the different MARS described from archaea to mammals, the mode of assembly of these complexes, and their roles in maintenance of cellular homeostasis.
    Mots-clés : Amino Acyl-tRNA Synthetases, Archaea, Biological Evolution, DBG, MARS, Phylogeny.
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Publications Principales avant 2015

- Dias, J., Renault, L., Pérez, J. and Mirande, M. (2013) Small-angle X-ray solution scattering study of the multi-aminoacyl-tRNA synthetase complex reveals an elongated and multi-armed particle. J. Biol. Chem. 288, 23979-23989.

- Dias, J., Octobre, G., Kobbi, L., Comisso, M., Flisiak, S. and Mirande, M. (2012) Activation of human mitochondrial lysyl-tRNA synthetase upon maturation of its premitochondrial perecursor. Biochemistry 51, 909-916.

- Kobbi, L., Octobre, G., Dias, J., Comisso, M. and Mirande, M. (2011) Association of mitochondrial lysyl-tRNA synthetase with HIV-1 GagPol involves catalytic domain of the synthetase and transframe and integrase domains of Pol. J. Mol. Biol. 410, 875-886.

- Havrylenko, S., Legouis, R., Negrutskii, B. and Mirande, M. (2011) Caenorhabditis elegans evolves a new architecture for the multi-aminoacyl-tRNA synthetase complex. J. Biol. Chem. 286, 28476-28487.

- Shalak, V., Kaminska, M. and Mirande, M. (2009) Translation initiation from two in-frame AUGs generates mitochondrial and cytoplasmic forms of the p43 component of the multisynthetase complex. Biochemistry 48, 9959-9968.

- Kaminska, M., Havrylenko, S., Decottignies, P., Le Marechal, P., Negrutskii, B. and Mirande, M. (2009) Dynamic organization of aminoacyl-tRNA synthetase complexes in the cytoplasm of human cells. J. Biol. Chem. 284, 13746-13754.

- Kaminska, M., Havrylenko, S., Decottignies, P., Gillet, S., Le Maréchal, P., Negrutskii, B. and Mirande, M. (2009) Dissection of the structural organization of the aminoacyl-tRNA synthetase complex. J. Biol. Chem. 284, 6053-6060.

- Shalak, V., Guigou, L., Kaminska, M., Wautier, M.P., Wautier, J.L. and Mirande, M. (2007) Characterization of p43(ARF), a derivative of the p43 component of multiaminoacyl-tRNA synthetase complex released during apoptosis. J. Biol. Chem. 282, 10935-10943.

- Mirande, M. (2007) The ins and outs of tRNA transport. EMBO Rep. 8, 547-549.

- Kaminska, M., Shalak, V., Francin, M. and Mirande, M. (2007) Viral hijacking of mitochondrial lysyl-tRNA synthetase. J. Virol. 81, 68-73.

- Mirande, M. (2005) Multi-Aminoacyl-tRNA Synthetase Complexes in The Aminoacyl-tRNA Synthetases (Ibba, M., Francklyn, C. & Cusack, S., eds) pp. 298-308, Landes Bioscience, Georgetown, Texas, USA.

- Guigou, L., Shalak, V. and Mirande, M. (2004) The tRNA-interacting factor p43 associates with mammalian arginyl-tRNA synthetase but does not modify its tRNA aminoacylation properties. Biochemistry 43, 4592-4600.

- Golinelli-Cohen, M.P., Zakrzewska, A. and Mirande, M. (2004) Complementation of yeast Arc1p by the p43 component of the human multisynthetase complex does not require its association with yeast MetRS and GluRS. J. Mol. Biol. 340, 15-27.

- Francin, M. and Mirande, M. (2003) Functional dissection of the eukaryotic-specific tRNA-interacting factor of lysyl-tRNA synthetase. J. Biol. Chem. 278, 1472-1479.

- Corti, O., Hampe, C., Koutnikova, H., Darios, F., Jacquier, S., Prigent, A., Robinson, J.C., Pradier, L., Ruberg, M., Mirande, M., Hirsch, E., Rooney, T., Fournier, A. and Brice, A. (2003) The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate : linking protein biosynthesis and neurodegeneration. Hum. Mol. Genet. 12, 1427-1437.

- Cans, C., Passer, B.J., Shalak, V., Nancy-Portebois, V., Crible, V., Amzallag, N., Allanic, D., Tufino, R., Argentini, M., Moras, D., Fiucci, G., Goud, B., Mirande, M., Amson, R. and Telerman, A. (2003) Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A. Proc. Natl. Acad. Sci. USA 100, 13892-13897.

- Francin, M., Kaminska, M., Kerjan, P. and Mirande, M. (2002) The N-terminal domain of mammalian lysyl-tRNA synthetase is a functional tRNA-binding domain. J. Biol. Chem. 277, 1762-1769.

- Shalak, V., Kaminska, M., Mitnacht-Kraus, R., Vandenabeele, P., Clauss, M. and Mirande, M. (2001) The EMAPII cytokine is released from the mammalian multisynthetase complex after cleavage of its p43/proEMAPII component. J. Biol. Chem. 276, 23769-23776.

- Renault, L., Kerjan, P., Pasqualato, S., Menetrey, J., Robinson, J.C., Kawaguchi, S., Vassylyev, D.G., Yokoyama, S., Mirande, M. and Cherfils, J. (2001) Structure of the EMAPII domain of human aminoacyl-tRNA synthetase complex reveals evolutionary dimer mimicry. EMBO J. 20, 570-578.

- Kaminska, M., Shalak, V. and Mirande, M. (2001) The appended C-domain of human methionyl-tRNA synthetase has a tRNA-sequestering function. Biochemistry 40, 14309-14316.

- Robinson, J.C., Kerjan, P. and Mirande, M. (2000) Macromolecular assemblage of aminoacyl-tRNA synthetases : quantitative analysis of protein-protein interactions and mechanism of complex assembly. J. Mol. Biol. 304, 983-994.

- Lazard, M., Kerjan, P., Agou, F. and Mirande, M. (2000) The tRNA-dependent activation of arginine by arginyl-tRNA synthetase requires inter-domain communication. J. Mol. Biol. 302, 991-1004.

- Kaminska, M., Deniziak, M., Kerjan, P., Barciszewski, J. and Mirande, M. (2000) A recurrent general RNA binding domain appended to plant methionyl-tRNA synthetase acts as a cis-acting cofactor for aminoacylation. EMBO J. 19, 6908-6917.

- Cahuzac, B., Berthonneau, E., Birlirakis, N., Guittet, E. and Mirande, M. (2000) A recurrent RNA binding domain is appended to eukaryotic aminoacyl-tRNA synthetases. EMBO J. 19, 445-452.

- Quevillon, S., Robinson, J.C., Berthonneau, E., Siatecka, S. and Mirande, M. (1999) Macromolecular assemblage of aminoacyl-tRNA synthetases : identification of protein-protein interactions and characterization of a core protein. J. Mol. Biol. 285, 183-196.

- Negrutskii, B.S., Shalak, V.F., Kerjan, P., El’skaya, A.V. and Mirande, M. (1999) Functional interaction of mammalian valyl-tRNA synthetase with elongation factor EF-1a in the complex with EF-1H. J. Biol. Chem. 274, 4545-4550.

- Lamour, V., Quevillon, S., Diriong, S., N’Guyen, v.C., Lipinski, M. and Mirande, M. (1994) Evolution of the Glx-tRNA synthetase family : The glutaminyl enzyme as a case of horizontal gene transfer. Proc. Natl Acad. Sci. USA 91, 8670-8674.

- Mirande, M. (1991) Aminoacyl-tRNA synthetase family from prokaryotes and eukaryotes : structural domains and their implications. Prog. Nucleic Acid Res. Mol. Biol. 40, 95-142.

- Cerini, C., Kerjan, P., Astier, M., Gratecos, D., Mirande, M. and Semeriva, M. (1991) A component of the multisynthetase complex is a multifunctional aminoacyl-tRNA synthetase. EMBO J. 10, 4267-4277.

- Mirande, M., Gache, Y., Corre, D.L. and Waller, J.P. (1982) Seven mammalian aminoacyl-tRNA synthetases co-purified as high molecular weight entities are associated within the same complex. EMBO J. 1, 733-736.

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