Research Groups

Marco Baralle

RNA Biology

Research Interests and Description
Group Members

Marco Baralle

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy

E-mail: barallemicgeb.org
Tel: +39-040-3757337
Office fax: +39-040-226555

Education

University College London, London, England, BSc Biochemistry, 1992
University of London, London, England, PhD, 2000

Career History

Since 2018, Group Leader, RNA Biology Group, ICGEB, Trieste, Italy
2013-2017, Group Leader, Biotechnology Development Group, ICGEB, Trieste, Italy
2003-2013, Research Scientist, Biotechnology Development Group, ICGEB, Trieste, Italy

Teaching Activity

Teaching and tutoring at the National Research Council of Buenos Aires, Argentina and at the Department of Biology, University of Buenos Aires, Argentina (1984-1986).

Scientific Activity

Current research interest focuses on the development of novel biotherapeutics for TDP 43 proteinopathies , and development of moncolanal biogenerics. He also is continuing his basic research on mechanisms of pre-mRNA processing in health and diseases and the evolutionary constraints in protein evolution derived from exonic splicing regulatory signals.

Marco Baralle is also an Academic Editor at PeerJ 

Selected Publications

De Conti, L., Baralle, M., Buratti, E. 2013. Exon and intron definition in pre-mRNA splicing. Wiley Interdiscip Rev RNA 1, 49-60

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

De Conti, L., Skoko, N., Buratti, E., Baralle, M. 2012. Complexities of 5'splice site definition: Implications in clinical analyses. RNA Biol 9

Passoni M, De Conti L, Baralle M, Buratti E. UG repeats/TDP-43 interactions near 5' splice sites exert unpredictable effects on splicing modulation. J Mol Biol 2012; 415:46-60.

Passoni M, De Conti L, Baralle M, Buratti E. UG repeats/TDP-43 interactions near 5' splice sites exert unpredictable effects on splicing modulation. J Mol Biol 2012; 415:46-60.

Skoko N, Baralle M, Tisminetzky S, Buratti E. InTRONs in biotech. Mol Biotechnol 2011; 48:290-7.

Ayala YM, De Conti L, Avendano-Vazquez SE et al. TDP-43 regulates its mRNA levels through a negative feedback loop. EMBO J 2011; 30:277-88.

Cox JJ, Sheynin J, Shorer Z et al. Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. Hum Mutat 2010; 31:E1670-86.

Buratti E, De Conti L, Stuani C et al. Nuclear factor TDP-43 can affect selected microRNA levels. FEBS J 2010; 277:2268-81.

Zago P, Baralle M, Ayala YM et al. Improving human interferon-beta production in mammalian cell lines by insertion of an intronic sequence within its naturally uninterrupted gene. Biotechnol Appl Biochem 2009; 52:191-8.

Skoko N, Baralle M, Buratti E, Baralle FE. The pathological splicing mutation c.6792C>G in NF1 exon 37 causes a change of tenancy between antagonistic splicing factors. FEBS Lett 2008; 582:2231-6.

Esperante SA, Rivolta CM, Miravalle L et al. Identification and characterization of four PAX8 rare sequence variants (p.T225M, p.L233L, p.G336S and p.A439A) in patients with congenital hypothyroidism and dysgenetic thyroid glands. Clin Endocrinol (Oxf) 2008; 68:828-35.

Baralle M, Pastor T, Bussani E, Pagani F. Influence of Friedreich ataxia GAA noncoding repeat expansions on pre-mRNA processing. Am J Hum Genet 2008; 83:77-88.

Baralle M, Baralle FE. Genetics and molecular biology: variations in alternative spliced pre-mRNA-protein isoforms and their role in disease. Curr Opin Lipidol 2008; 19:429-30.

Buratti E, Chivers M, Kralovicova J et al. Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Nucleic Acids Res 2007; 35:4250-63.

Baralle M, Baralle FE. Genetics and molecular biology: micro RNAs are welcome to the lipid field. Curr Opin Lipidol 2007; 18:375-7.

Dominissini S, Buratti E, Bembi B et al. Characterization of two novel GBA mutations causing Gaucher disease that lead to aberrant RNA species by using functional splicing assays. Hum Mutat 2006; 27:119.

Buratti E, Baralle M, Baralle FE. Defective splicing, disease and therapy: searching for master checkpoints in exon definition. Nucleic Acids Res 2006; 34:3494-510.

Baralle M, Skoko N, Knezevich A et al. NF1 mRNA biogenesis: effect of the genomic milieu in splicing regulation of the NF1 exon 37 region. FEBS Lett 2006; 580:4449-56.

Baralle M, Baralle FE. Genetics and molecular biology: single nucleotide polymorphism associations and their functional significance. Curr Opin Lipidol 2006; 17:360-2.

Baralle M, Baralle FE. Genetics and molecular biology. Curr Opin Lipidol 2005; 16:385-7.

Baralle D, Baralle M. Splicing in action: assessing disease causing sequence changes. J Med Genet 2005; 42:737-48.

Zhang L, Vincent GM, Baralle M et al. An intronic mutation causes long QT syndrome. J Am Coll Cardiol 2004; 44:1283-91.

Buratti E, Baralle M, De Conti L et al. hnRNP H binding at the 5' splice site correlates with the pathological effect of two intronic mutations in the NF-1 and TSHbeta genes. Nucleic Acids Res 2004; 32:4224-36.

Baralle M, Baralle FE. Vascular gene therapy: getting to know the players, avoiding the pitfalls. Curr Opin Lipidol 2004; 15:479-81.

Baralle M, Baralle D, De Conti L et al. Identification of a mutation that perturbs NF1 agene splicing using genomic DNA samples and a minigene assay. J Med Genet 2003; 40:220-2.

Baralle M, Baralle FE. Genetics and molecular biology. Curr Opin Lipidol 2001; 12:663-5.

Baralle M, Baralle FE. Genetics and molecular biology. Curr Opin Lipidol 2000; 11:653-6.

Vergnes L, Baroukh N, Lehy T et al. Human apolipoprotein A-IV reduces gastric acid secretion and diminishes ulcer formation in transgenic mice. FEBS Lett 1999; 460:178-81.

Baralle M, Vergnes L, Muro AF et al. Regulation of the human apolipoprotein AIV gene expression in transgenic mice. FEBS Lett 1999; 445:45-52.

Baralle M, Baralle FE. Genetics and molecular biology. Curr Opin Lipidol 1999; 10:365-8.

 

BOOK CHAPTERS

Splicing mechanisms in the NF1 gene. Marco Baralle and Diana Baralle. Human Molecular Genetics. Meena Upadhyaya,David Cooper In press

From Bedside to bench: How to Analyse a Splicing Mutation. Baralle M, Baralle D. Alternative pre-mRNA splicing: Theory and Protocols. Stamm S., Smith C.W., Lurhmann R. (Eds.) pp. 3 (2012) Wiley-VCH, Weinheim

Protein splicing. Baralle M. and Buratti E. Encyclopedia of Genetics, 2nd edition (2012) Mitchell S. (Ed.)

Research Groups

Francisco E. Baralle

RNA Biology

Research Interests and Description
Group Members

Francisco E. Baralle

Former Director-General, ICGEB

International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy

E-mail: baralleicgeb.org
Office tel: +39-040-3757337
Lab tel: +39-040-3757316
Office fax: +39-040-3757361

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 in 2004 became the Director-General of the same institute. 

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

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

Baralle, F.E., Buratti, E. 2011. TDP-43: Overview of the series. FEBS J. 278(19), 3529

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

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

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