Makarov, Evgeny - Brunel University - Department of Life Sciences, Biomedical Sciences

个人简介

2007: Lecturer, Division of Biosciences, School of Health Sciences and Social Care, Brunel University London. 2005-2007: Research Associate, Department of Biochemistry, University of Leicester. 1998-2000: Post-doctoral researcher, Max-Planck-Institut für Biophysikalische Chemie, G?ttingen, Germany. 1997-2000: Post-doctoral researcher, Institut für Molekularbiologie und Tumorforschung, Philipps-Universit?t, Marburg, Germany 1994 -1997: Research Associate, Department of Biochemistry, University of Leicester,UK 1993 -1994: CNRS researcher, Laboratoire de Génétique Moléculaire, Ecole Normale Supérieure, Paris, France 1991 -1993: Post-doctoral researcher, Department of Biological Chemistry, School of Medicine, University of California, Davis, USA. 1990 -1991: Post-doctoral researcher, Department of Molecular Microbiology, School of Medicine, Washington University, St. Louis, USA 1980 -1990: Research scientist, Department of Molecular and Radiation Biophysics, Leningrad Nuclear Physics Institute, Gatchina, USSR

研究领域

My research interests are in the field of precursor messenger RNA (pre-mRNA) splicing. Pre-mRNA splicing is a cellular process in which non-coding sequences (introns) are removed and coding sequences (exons) are joined together to generate mRNA for protein production. Pre-mRNA splicing is somewhat similar to film editing: if it is not done properly, two unmatched scenes may be stitched together in one episode, which would not make sense. In splicing, if exon-intron boundaries (splice sites) are not correctly identified, the wrong mRNA will be produced. From this a faulty protein will be synthesised and this may cause disease. To extend the analogy, a film scenario is dramatically changed by the selection of scenes; by the same token, in a living cell, pre-mRNA can be processed in different ways via the alternative use of different splice sites. This phenomenon is called alternative splicing and allows the production of several proteins from a single gene. I am currently focused on the study of disease-associated alternative splicing. The major ongoing project is on the study of the ageing-related pre-mRNA splicing of human LMNA gene, encoding lamin A and C proteins, and especially, its aberrant splicing that causes the premature ageing of Hutchinson Gilford Progeria Syndrome patients. The aim is to identify the proteins modulating the specific splicing outcomes which, in turn, are likely to affect the speed of the ageing process. In this respect, the pharmaceutical targeting of the proteins identified in the proposed research -- inhibition of their function by small interacting molecules -- may lead to the discovery of novel drugs capable of slowing the ageing process. The other ongoing projects are: (i) The study of SCLC (small cell lung cancer) associated alternative splicing of actinine-4 pre-mRNA; (ii) The hTERT alternative splicing regulation as a potential cancer therapeutic modality.

近期论文

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Makarov, E. and Makarova, O. (2015) 'The 35S U5 snRNP Is Generated from the Activated Spliceosome during In vitro Splicing.'. PLoS One, 10 (5). Download publication Shtam, TA. , Kovalev, RA. , Varfolomeeva, EY. , Makarov, EM. , et al. (2013) 'Exosomes are natural carriers of exogenous siRNA to human cells in vitro'. Cell Communication and Signaling, 11 (1). doi: 10.1186/1478-811X-11-88 Download publication Girard, C. , Will, CL. , Peng, J. , Makarov, EM. , et al. (2012) 'Post-transcriptional spliceosomes are retained in nuclear speckles until splicing completion.'. Nature Communications, 3 doi: 10.1038/ncomms1998 Makarov, EM. , Owen, N. , Bottrill, A. and Makarova, OV. (2012) 'Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs'. Nucleic Acids Research, 40 (6). pp. 2639 - 2652. doi: 10.1093/nar/gkr1056 Download publication Bridger, JM. , Eskiw, CH. , Makarov, EM. , Tree, D. and Kill, IR. (2011) 'Progeria Research Day at Brunel University'. Nucleus, 2 (6). pp. 1 - 6. Abbaszadeh, F. , Clingen, PH. , Arlett, C. , Plowman, PN. , et al. (2010) 'A novel splice variant of the DNA-PKcs gene is associated with clinical and cellular radiosensitvity in a xeroderma pigmentosum patient'. Journal of Medical Genetics, 46 (11). pp. 1 - 24. doi: 10.1136/jmg.2009.068866 Download publication Bujakowska, K. , Maubaret, C. , Chakarova, CF. , Tanimoto, N. , et al. (2009) 'Study of gene-targeted mouse models of splicing factor gene Prpf31 implicated in human autosomal dominant retinitis pigmentosa (RP)'. Investigative Ophthalmology and Visual Science, 50 (12). pp. 5927 - 5933. doi: 10.1167/iovs.08-3275 Hernández, H. , Makarova, OV. , Makarov, EM. , Morgner, N. , et al. (2009) 'Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP'. PLoS ONE, 4 (9). doi: 10.1371/journal.pone.0007202 Download publication Sander, B. , Golas, MM. , Makarov, EM. , Brahms, H. , et al. (2006) 'Organization of core spliceosomal components U5 snRNA loop I and U4/U6 di-snRNP within U4/U6.U5 tri-snRNP as revealed by electron cryomicroscopy'. Molecular Cell, 24 (2). pp. 267 - 278. doi: 10.1016/j.molcel.2006.08.021 Laggerbauer, B. , Liu, S. , Makarov, E. , Vornlocher, HP. , et al. (2005) 'The human U5 snRNP 52K protein (CD2BP2) interacts with U5-102K (hPrp6), a U4/U6.U5 tri-snRNP bridging protein, but dissociates upon tri-snRNP formation'. RNA, 11 (5). pp. 598 - 608. doi: 10.1261/rna.2300805 Makarova, OV. , Makarov, EM. , Urlaub, H. , Will, CL. , et al. (2004) 'A subset of human 35S U5 proteins, including Prp19, function prior to catalytic step 1 of splicing'. The EMBO Journal, 23 (12). pp. 2381 - 2391. doi: 10.1038/sj.emboj.7600241 Boehringer, D. , Makarov, EM. , Sander, B. , Makarova, OV. , et al. (2004) 'Three-dimensional structure of a pre-catalytic human spliceosomal complex B'. Nature Structural & Molecular Biology, 11 (5). pp. 463 - 468. doi: 10.1038/nsmb761 Makarov, EM. , Makarova, OV. , Urlaub, H. , Gentzel, M. , et al. (2002) 'Small nuclear ribonucleoprotein remodeling during catalytic activation of the spliceosome'. Science, 298 (5601). pp. 2205 - 2208. doi: 10.1126/science.1077783 Dellaire, G. , Makarov, EM. , Cowger, JJ. , Longman, D. , et al. (2002) 'Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes'. Mol Cell Biol, 22 (14). pp. 5141 - 5156. doi: 10.1128/MCB.22.14.5141-5156.2002 Schneider, C. , Will, CL. , Makarova, OV. , Makarov, EM. and Lührmann, R. (2002) 'Human U4/U6.U5 and U4atac/U6atac.U5 tri-snRNPs exhibit similar protein compositions'. Molecular and Cellular Biology, 22 (10). pp. 3219 - 3229. doi: 10.1128/?MCB.22.10.3219-3229.2002 Makarova, OV. , Makarov, EM. , Liu, SB. , Vornlocher, HP. and Luhrmann, R. (2002) 'Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6 center dot U5 tri-snRNP formation and pre-mRNA splicing'. EMBO JOURNAL, 21 (5). pp. 1148 - 1157. doi: 10.1093/emboj/21.5.1148 Makarova, OV. , Makarov, EM. and Luhrmann, R. (2001) 'The 65 and 110 kDa SR-related proteins of the U4/U6 center dot U5 tri-snRNP are essential for the assembly of mature spliceosomes'. EMBO JOURNAL, 20 (10). pp. 2553 - 2563. doi: 10.1093/emboj/20.10.2553 Makarov, EM. , Makarova, OV. , Achsel, T. and Lührmann, R. (2000) 'The human homologue of the yeast splicing factor Prp6p contains multiple TPR elements and is stably associated with the U5 snRNP via protein-protein interactions.'. J Mol Biol, 298 (4). pp. 567 - 575. Venables, JP. , Elliott, DJ. , Makarova, OV. , Makarov, EM. , et al. (2000) 'RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2 beta and affect splicing'. HUMAN MOLECULAR GENETICS, 9 (5). pp. 685 - 694. doi: 10.1093/hmg/9.5.685 Elliott, DJ. , Oghene, K. , Makarov, G. , Makarova, O. , et al. (1998) 'Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development.'. Journal of cell science, 111 ( Pt 9) pp. 1255 - 1265. Makarova, OV. , Makarov, EM. , Sousa, R. and Dreyfus, M. (1995) 'Transcribing of Escherichia coli genes with mutant T7 RNA polymerases: Stability of lacZ mRNA inversely correlates with polymerase speed'. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 92 (26). pp. 12250 - 12254. doi: 10.1073/pnas.92.26.12250