Education
Prof. Francisco E. Baralle gained his BSc and PhD in Chemistry at the University of Buenos Aires and his degree in Medicine and Surgery at the University of Naples.
Career History
After completing his Ph.D. studies at the Department of Organic Chemistry, he transferred to the Instituto de Investigaciones Bioquimicas Fundacion Campomar directed by Prof. Luis F. Leloir. In 1974, he moved to the MRC Laboratory of Molecular Biology, Cambridge, UK, where he worked in the Division directed by Dr. Frederick Sanger. From 1980 to 1990, he was University Lecturer of Pathology at Oxford and Fellow of Magdalen College. In 1980, he was elected member of the European Molecular Biology Organisation (EMBO). In 1993, he was awarded the Platinum Konex Prize for Science and Technology (Argentina) as the best scientist of the decade in Genetic and Cytology and in 2001 he was elected Member of the Argentine Academy of Sciences. In September 1990, he was appointed Director of the Trieste Component of ICGEB and from 2004-2014 was the Director-General of the ICGEB.
Scientific Activity
In 1977, Prof. Baralle published the sequence of the messenger RNA coding for beta-globin, the first complete primary structure of an eukaryotic mRNA. In 1979, his group isolated the gene for epsilon-globin, a component of the human embryonic haemoglobin. He has also contributed to the study of the genetic factors involved in the susceptibility to hypertension, atherosclerosis and coronary heart disease.
He was one of the first to describe the pre-mRNA alternative splicing process in the 1980s and since then he has made critical contributions to understanding the molecular mechanisms involved in this important cellular process in health and disease. Prof. Baralle heads the mis splicing and disease project within the European RNA alternative splicing network of excellence (EURASNET) that involves close European collaborations in basic and clinical research.
Furthermore, in addition to the basic research fields mentioned above, applied biotechnology projects are being carried out at the ICGEB laboratory. In particular, strains and process protocols have been developed for the production of recombinant biopharmaceuticals.
Selected publications
Bembich, S., Herzog, J., De Conti, L., Stuani, C., Avendaño-Vasquez, S.E., Buratti, E., Baralle, M., Baralle, F.E. 2014. Predominance of spliceosomal complex formation over polyadenylation site selection in TDP-43 autoregulation. Nucleic Acids Res 42, 3362-3371 PubMed link
Lukavsky, P.J., Daujotyte, D., Tollervey, J.R., Ule, J., Stuani, C., Buratti, E., Baralle, F.E., Damberger, F.F., Allain, F.H. 2013. Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43. Nat Struct Mol Biol 20, 1443-1449 PubMed link
Avendaño-Vázquez, S.E., Dhir, A., Bembich, S., Buratti, E., Proudfoot, N., Baralle, F.E. 2012. Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing and alternative polyA site selection. Genes Dev 26, 1679-1684 PubMed link
Budini, M., Buratti, E., Stuani, C., Guarnaccia, C., Romano, V., De Conti, L., Baralle, F.E. 2012. A cellular model of TAR DNA Binding Protein 43 (TDP-43) aggregation based on its C-terminal Q/N rich region. J. Biol. Chem. 287(10), 7512-7525
Budini, M., Romano, V., Bembich, S., Avendaño-Vázquez, S.E., Buratti, E., Baralle, F.E. 2012. Role of selected mutations in the Q/N rich region of TDP-43 in EGFP-12xQ/N-induced aggregate formation. Brain Res. 1462, 139-150
Buratti, E., Baralle, F.E. 2012. TDP43: gumming up neurons through protein-protein and protein-RNA interactions. Trends Biochem. Sci. 37(6), 237-247
Colombrita, C., Onesto, E., Megiorni, F., Pizzuti, A., Baralle, F.E., Buratti, E., Silani, V., Ratti, A. 2012. TDP-43 and FUS RNA-binding proteins bind distinct sets of cytoplasmic messenger RNAs and differently regulate their post-transcriptional fate in motoneuron-like cells. J. Biol. Chem. 287(19), 15635-15647
Lukavsky, P.J., Daujotyte, D., Tollervey, J.R., Ule, J., Stuani, C., Buratti, E., Baralle, F.E., Damberger, F.F., Allain, F.H. 2013. Molecular basis of UG-rich RNA recognition by the human splicing factor TDP-43. Nat Struct Mol Biol 20, 1443-1449 PubMed link
Avendaño-Vázquez, S.E., Dhir, A., Bembich, S., Buratti, E., Proudfoot, N., Baralle, F.E. 2012. Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing and alternative polyA site selection. Genes Dev 26, 1679-1684 PubMed link
Budini, M., Buratti, E., Stuani, C., Guarnaccia, C., Romano, V., De Conti, L., Baralle, F.E. 2012. A cellular model of TAR DNA Binding Protein 43 (TDP-43) aggregation based on its C-terminal Q/N rich region. J. Biol. Chem. 287(10), 7512-7525
Budini, M., Romano, V., Bembich, S., Avendaño-Vázquez, S.E., Buratti, E., Baralle, F.E. 2012. Role of selected mutations in the Q/N rich region of TDP-43 in EGFP-12xQ/N-induced aggregate formation. Brain Res. 1462, 139-150
Buratti, E., Baralle, F.E. 2012. TDP43: gumming up neurons through protein-protein and protein-RNA interactions. Trends Biochem. Sci. 37(6), 237-247
Colombrita, C., Onesto, E., Megiorni, F., Pizzuti, A., Baralle, F.E., Buratti, E., Silani, V., Ratti, A. 2012. TDP-43 and FUS RNA-binding proteins bind distinct sets of cytoplasmic messenger RNAs and differently regulate their post-transcriptional fate in motoneuron-like cells. J. Biol. Chem. 287(19), 15635-15647
Ćurlin, M., Kapuralin, K., Muro, A.F., Baralle, F.E., Chowdury, K., Gajović, S. 2012. Stam2 expression pattern during embryo development. Gene Expr. Patterns 12(1-2), 68-76
Zubovic, L., Baralle, M., Baralle, F.E. 2012. Mutually exclusive splicing regulates the Nav 1.6 Sodium channel function through a combinatorial mechanism that involves three distinct splicing regulatory elements and their ligands. Nucleic Acids Res 40, 6255-6269 PubMed link
Ayala, Y.M., De Conti, L., Avendaño-Vázquez, S.E., Dhir, A., Romano, M., D’Ambrogio, A., Tollervey, J., Ule, J., Baralle, M., Buratti, E., Baralle, F.E. 2011. TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J. 30, 277-288
Budini, M., Baralle, F.E., Buratti, E. 2011. Regulation of gene expression by TDP-43 and FUS/TLS in Frontotemporal Lobar Degeneration. Curr. Alzheimer Res. 8(3), 237-245
Buratti, E., Baralle, F.E. 2011. TDP-43: New aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease. FEBS J. 278(19), 3530-3538
Godena, V.K., Romano, G., Romano, M., Appocher, C., Klima, R., Buratti, E., Baralle, F.E., Feiguin, F. 2011. TDP-43 regulates Drosophila neuromuscular junctions growth by modulating Futsch/MAP1B levels and synaptic microtubules organisation. PLoS One 6(3), e17808
Zago, P., Buratti, E., Stuani, C., Baralle, F.E. 2011. Evolutionary connections between coding and splicing regulatory regions in the fibronectin EDA exon. J. Mol. Biol. 411, 1-15
Buratti, E., Baralle, F.E. 2010. Neurons don’t appreciate FUSsing in the cytoplasm. EMBO J. 29, 2769-2771
Buratti, E., Baralle, F.E. 2010. The multiple roles of TDP 43 in pre mRNA processing and gene expression regulation. RNA Biol. 7(4), 420-429
Buratti, E., De Conti, L., Stuani, C., Romano, M., Baralle, M., Baralle, F.E. 2010. Nuclear factor TDP-43 can affect selected microRNA levels. FEBS J. 277, 2268-2281
Dhir, A., Buratti, E., van Santen, M.A., Lührmann, R., Baralle, F.E. 2010. The intronic splicing code: multiple factors involved in ATM pseudoexon definition. EMBO J 29, 749-760 PubMed link
Haque, A., Buratti, E., Baralle, F.E. 2010. Functional properties and evolutionary splicing constraints on a composite exonic regulatory element of splicing in CFTR exon 12. Nucleic Acids Res. 38(2), 647-659
Sorarù, G., Orsetti, V., Buratti, E., Baralle, F.E., Cima, V., Volpe, M., D’Ascenzo, C., Palmieri, A., Koutsikos, K., Pegoraro, E., Angelini, C. 2010. TDP-43 in skeletal muscle of patients affected with Amyotrophic Lateral Sclerosis. Amyotroph. Lateral Scler. 11(1-2), 240-243
Buratti, E., Baralle, F.E. 2011. TDP-43: New aspects of autoregulation mechanisms in RNA binding proteins and their connection with human disease. FEBS J. 278(19), 3530-3538
Godena, V.K., Romano, G., Romano, M., Appocher, C., Klima, R., Buratti, E., Baralle, F.E., Feiguin, F. 2011. TDP-43 regulates Drosophila neuromuscular junctions growth by modulating Futsch/MAP1B levels and synaptic microtubules organisation. PLoS One 6(3), e17808
Zago, P., Buratti, E., Stuani, C., Baralle, F.E. 2011. Evolutionary connections between coding and splicing regulatory regions in the fibronectin EDA exon. J. Mol. Biol. 411, 1-15
Buratti, E., Baralle, F.E. 2010. Neurons don’t appreciate FUSsing in the cytoplasm. EMBO J. 29, 2769-2771
Buratti, E., Baralle, F.E. 2010. The multiple roles of TDP 43 in pre mRNA processing and gene expression regulation. RNA Biol. 7(4), 420-429
Buratti, E., De Conti, L., Stuani, C., Romano, M., Baralle, M., Baralle, F.E. 2010. Nuclear factor TDP-43 can affect selected microRNA levels. FEBS J. 277, 2268-2281
Dhir, A., Buratti, E., van Santen, M.A., Lührmann, R., Baralle, F.E. 2010. The intronic splicing code: multiple factors involved in ATM pseudoexon definition. EMBO J 29, 749-760 PubMed link
Haque, A., Buratti, E., Baralle, F.E. 2010. Functional properties and evolutionary splicing constraints on a composite exonic regulatory element of splicing in CFTR exon 12. Nucleic Acids Res. 38(2), 647-659
Sorarù, G., Orsetti, V., Buratti, E., Baralle, F.E., Cima, V., Volpe, M., D’Ascenzo, C., Palmieri, A., Koutsikos, K., Pegoraro, E., Angelini, C. 2010. TDP-43 in skeletal muscle of patients affected with Amyotrophic Lateral Sclerosis. Amyotroph. Lateral Scler. 11(1-2), 240-243
Valacca, C., Bonomi, S., Buratti, E., Pedrotti, S., Baralle, F.E., Sette, C., Ghigna, C., Biamonti, G. 2010. Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J. Cell Biol. 191(1), 87-99
Buratti, E., Baralle, F.E. 2009. The molecular links between TDP-43 dysfunction and neurodegeneration. Adv. Genet. 66, 1-34
Corrado, L., Ratti, A., Gellera, C., Buratti, E., Castellotti, B., Carlomagno, Y., Ticozzi, N., Mazzini, L., Testa, L., Taroni, F., Baralle, F.E., Silani, V., D’Alfonso, S. 2009. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis. Hum. Mutat. 30(4), 688-694
D’Ambrogio, A., Buratti, E., Stuani, C., Guarnaccia, C., Romano, M., Ayala, Y.M., Baralle, F.E. 2009. Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo. Nucleic Acids Res. 37(12), 4116-4126
Feiguin, F., Godena, V.K., Romano, G., D’Ambrogio, A., Klima, R., Baralle, F.E. 2009. Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior. FEBS Lett. 583, 1586-1592
Marcucci, R., Romano, M., Feiguin, F., O’Connell, M., Baralle, F.E. 2009. Dissecting the splicing mechanism of the Drosophila editing enzyme; dADAR. Nucleic Acids Res. 37(5), 1663-1671
Nonaka, T., Arai, T., Buratti, E., Baralle, F.E., Akiyama, H., Hasegawa, M. 2009. Phosphorylated and ubiquitinated TDP-43 pathological inclusions in ALS and FTLD-U are recapitulated in SH-SY5Y cells. FEBS Lett. 583, 394-400
Zhang, Y.J., Xu, Y.F., Cook, C., Gendron, T.F., Roettges, P., Link, C.D., Lin, W.L., Tong, J., Castanedes-Casey, M., Ash, P., Gass, J., Rangachari, V., Buratti, E., Baralle, F.E., Golde, T.E., Dickson, D.W., Petrucelli, L. 2009. Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity. Proc. Natl. Acad. Sci. USA 106(18), 7607-7612
Ayala, Y., Misteli, T., Baralle, F.E. 2008. TDP-43 regulates retinoblastoma protein phosphorylation through the repression of cyclin-dependent kinase 6 expression. Proc. Natl. Acad. Sci. USA 105, 3785-3789
Ayala, Y.M., Zago, P., D’Ambrogio, A., Xu, Y.F., Petrucelli, L., Buratti, E., Baralle, F.E. 2008. Structural determinants of the cellular localization and shuttling of TDP-43. J. Cell Sci. 121, 3778-3785 PubMed link
Babaev, V.R., Porro, F., Linton, M.F., Fazio, S., Baralle, F.E., Muro, A.F. 2008. Absence of regulated splicing of fibronectin EDA exon reduces atherosclerosis in mice. Atherosclerosis 197, 534–540
Baralle, M., Baralle, F.E. 2008. Genetics and molecular biology: Variations in alternative spliced pre-mRNA-protein isoforms and their role in disease. Curr. Opin. Lipidol. 19, 429-430
Buratti, E., Baralle, F.E. 2008. Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front. Biosci. 13, 867-878
Chauhan, A.K., Kisucka, J., Cozzi, M.R., Walsh, M.T., Moretti, F.A., Battiston, M., Mazzucato, M., De Marco, L., Baralle, F.E., Wagner, D.D., Muro, A.F. 2008. Prothrombotic effects of fibronectin isoforms containing the EDA domain. Arterioscler. Thromb. Vasc. Biol. 28, 296-301
Hasegawa, M., Arai, T., Nonaka, T., Kametani, F., Yoshida, M., Hashizume, Y., Beach, T.G., Buratti, E., Baralle, F., Morita, M., Nakano, I., Oda, T., Tsuchiya, K., Akiyama, H. 2008. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann. Neurol. 64, 60-70
Inukai, Y., Nonaka, T., Arai, T., Yoshida, M., Hashizume, Y., Beach, T.G., Buratti, E., Baralle, F.E., Akiyama, H., Hisanaga, S.I., Hasegawa, M. 2008. Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS. FEBS Lett. 582, 2899-290
Muro, A.F., Moretti, F.A., Moore, B.B., Yan, M., Atrasz, R.G., Wilke, C.A., Flaherty, K.R., Martinez, F.J., Tsui, J.L., Sheppard, D., Baralle, F.E., Toews, G.B., White, E.S. 2008. An essential role for fibronectin extra type III domain A in pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 177, 638-45
Romano, M., Bacalini, M.G., Verschoor, E.J., Crovella, S., Baralle, F.E. 2008. Origin and evolution of the c.844_845ins68/c.833T>C mutations within the cystathionine beta-synthase gene in great apes. FEBS Lett. 582, 423-426
Skoko, N., Baralle, M., Buratti, E., Baralle, F.E. 2008. The pathological splicing mutation c.6792C>G in NF1 exon 37 causes a change of tenancy between antagonistic splicing factors. FEBS Lett. 582, 2231–2236
Sreedharan, J., Blair, I.P., Tripathi, V.B., Hu, X., Vance, C., Rogelj, B., Ackerley, S., Durnall, J.C., Williams, K.L., Buratti, E., Baralle, F.E., de Belleroche, J., Mitchell, J.D., Leigh, P.N., Al-Chalabi, A., Miller, C.C., Nicholson, G., Shaw, C.E. 2008. TDP-43 mutations in familial and sporadic Amyotrophic Lateral Sclerosis. Science 319, 1668-1672
White, E.S., Baralle, F.E., Muro, A.F. 2008. New insights into form and function of fibronectin splice variants. J. Pathol. 216, 1-14
Baralle, M., Baralle, F.E. 2007. Genetics and molecular biology: micro RNAs are welcome to the lipid field. Curr. Opin. Lipidol. 18, 375-377
Buratti, E., Dhir, A., Lewandowska, M.A., Baralle, F.E. 2007. RNA structure is a key regulatory element in pathological ATM and CFTR pseudoexon inclusion events. Nucleic Acids Res. 35, 4369-4383
Buratti, E., Stuani, C., De Prato, G., Baralle, F.E. 2007. SR protein-mediated inhibition of CFTR exon 9 inclusion: molecular characterisation of the intronic splicing silencer. Nucleic Acids Res. 35, 4359-4368
Giraud, M., Taubert, R., Vandiedonck, C., Ke, X., Lévi-Strauss, M., Pagani, F., Baralle, F.E., Eymard, B., Tranchant, C., Gajdos, P., Vincent, A., Willcox, N., Beeson, D., Kyewski, B., Garchon, H.J. 2007. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature 448, 934-937
Marcucci, R., Baralle, F.E., Romano, M. 2007. Complex splicing control of the human Thrombopoietin gene by intronic G runs. Nucleic Acids Res. 35, 132-142
Moretti, F.A., Chauhan, A.K., Iaconcig, A., Porro, F., Baralle, F.E., Muro, A.F. 2007. A major fraction of fibronectin present in the extracellular matrix of tissues is plasma-derived. J. Biol. Chem. 282, 28057-28062
Raponi, M., Baralle, F.E., Pagani, F. 2007. Reduced splicing efficiency induced by synonymous substitutions may generate a substrate for natural selection of new splicing isoforms: the case of CFTR exon 12. Nucleic Acids Res. 35, 606-613
Zhang, Y.J., Xu, Y.F., Dickey, C.A., Buratti, E., Baralle, F.E., Bailey, R., Pickering-Brown, S., Dickson, D., Petrucelli, L. P. 2007. rogranulin mediates caspase-dependent cleavage of TAR DNA binding protein-43. J. Neurosci. 27, 10530-10534