Cargo Conicet: Investigador Superior
Área: Biología Molecular y Celular
Tema de Trabajo: Regulación del splicing alternativo del ARN mensajero
Descripción de trabajo: Trabajamos en la regulación del splicing alternativo (SA) del ARN mensajero, explicando cómo un único gen es capaz de generar muchas proteínas. Encontramos que cambios en la velocidad de la transcripción producidos en células animales por el daño del DNA o por modificaciones de la cromatina, y en plantas por la luz, controlan el SA. Vimos que drogas que afectan la estructura de la cromatina corrigen un defecto en el SA que puede derivar en una terapia de la atrofia muscular espinal en humanos.

Pérez MV, Guerrero LD, Orellana E, Figuerola EL, Erijman L (2019) Time-series genome-centric analysis unveils bacterial response to operational disturbance in activated sludge. mSystems 4: e00169-19

Orellana E, Davies-Sala C, Guerrero LD, Vardé I, Altina M, Lorenzo MC, Figuerola EL, Pontiggia R, Erijman L (2019) Microbiome network analysis of co-occurrence patterns in anaerobic co-digestion of sewage sludge and food waste. Water Science and Technology 79, 1956

Guijarro-Hernandez K, Aparicio V, de Gerónimo E, Castellote M, Figuerola EL, Costa JL, Erijman, L (2018). Soil microbial communities and glyphosate decay in soils with different herbicide application history. The Science of Total Environment 634, 974

– Kornblihtt, A. R., Vibe-Pedersen, K. & Baralle, F. E. Isolation and characterization of cDNA clones for human and bovine fibronectins. Proc. Natl. Acad.Sci.USA 80, 3218-3222 (1983).

– Kornblihtt, A. R., Vibe-Pedersen, K. & Baralle, F. E. Human fibronectin: molecular cloning evidence for two mRNA species differing by an internal segment coding for a structural domain. EMBO J. 3, 221-226 (1984).

– Kornblihtt, A. R., Umezawa, K., Vibe-Pedersen, K. & Baralle, F. E. Primary structure of human fibronectin: differential splicing may generate at least 10 polypeptides from a single gene. EMBO J. 4, 1755-1759 (1985).

– Gutman, A. & Kornblihtt, A. R. Identification of a third region of cell-specific alternative splicing in human fibronectin mRNA. Proc. Natl. Acad.Sci.USA 84, 7179-7182 (1987).

– Cramer, P., Pesce, C. G., Baralle, F. E. & Kornblihtt, A. R. Functional association between promoter architecture and transcript alternative splicing. Proc. Natl. Acad. Sci. USA 94,, 11456-11460 (1997).

– Melen, G. J., Pesce, C. G., Rossi, M. S. & Kornblihtt, A. R. Novel processing in a mammalian nuclear 28S pre-rRNA: tissue-specific elimination of an “intron” bearing a hidden break site. EMBO J. 18, 3107-3118 (1999).

– Cramer, P., Cáceres, J., Cazalla, D., Kadener, S., Muro, A. F., Baralle, F. E. & Kornblihtt, A. R. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer. Molecular Cell 4, 251-258 (1999).

– Kadener, S., Cramer, P., Nogués, G., Cazalla, D., de la Mata, M., Fededa, J. P., Werbajh, S., Srebrow, A. & Kornblihtt, A. R. Antagonistic effects of T-Ag and VP16 reveal a role for RNA pol II elongation on alternative splicing. EMBO J. 20, 5759-5768 (2001).

– Cáceres, J. F. & Kornblihtt, A. R. Alternative splicing regulation: multiple control mechanisms and involvement in human disease. Trends Genet. 18, 186-193 (2002).

– Kadener, S., Fededa, J. P., Rosbash, M. & Kornblihtt, A. R. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation. Proc. Natl. Acad. Sci. USA 99, 8185-8190 (2002). Selected as “must read” (factor 3) in Faculty of 1000. – de la Mata, M., Alonso, C. R., Kadener, S., Fededa, J. P., Blaustein, M., Pelisch, F., Cramer, P., Bentley, D., & Kornblihtt, A. R. A slow RNA polymerase II affects alternative splicing in vivo. Molecular Cell 12, 525-532 (2003). Commented as News and Views in Nature Struct. Mol. Biol. 10, 876-878 (2003). Selected as “exceptional” (factor 9) in Faculty of 1000.

– Fededa, J. P., Petrillo, E., Gelfand, M. S., Neverov, A. D., Kadener, S., Nogués, G., Pelisch, F., Baralle, F. E., Muro, A. F., and Kornblihtt, A. R. A polar mechanism coordinates different regions of alternative splicing within a single gene. Molecular Cell. 19, 393-404 (2005)

– de la Mata, M. & Kornblihtt, A. R. RNA polymerase II C-terminal domain mediates regulation of alternative splicing by SRp20. Nature Struct. Mol. Biol. 13, 973-980 (2006). Commented as News and Views in Nature Struct. Mol. Biol. 13, 952-953, 2006. Selected in Faculty of 1000. Cover of the issue.

– Schor, I. E., Rascovan, N., Pelisch, F., Alló, M. & Kornblihtt, A. R. Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing. Proc. Natl. Acad. Sci. USA 106, 4325-4330 (2009).

– Muñoz, M. J., Pérez Santangelo, S., Paronetto, M. P., de la Mata, M., Pelisch, F., Boireau, S., Glover-Cutter K., Ben-Dov, C., Blaustein, M., Lozano, J. J., Bird, G., Bentley, D., Bertrand, E. & Kornblihtt, A. R. DNA damage regulates alternative splicing through inhibition of RNA polymerase II elongation. Cell 137, 708-720 (2009). Commented as Leading Edge in Cell 137, 600-602 (2009).

– Alló, M., Buggiano, V., Fededa, J. P., Petrillo, E., Schor, I., de la Mata, M., Agirre, E., Plass, M., Eyras, E., Abou Elela, S., Klinck, R., Chabot, B. & Kornblihtt, A. R. Control of alternative splicing through siRNA-mediated transcriptional gene silencing. Nature Struct. Mol. Biol. 16, 717-724 (2009).

– Sánchez, S. E.*, Petrillo, E.*, Beckwith, E. J., Zhang, X., Matías, L., Rugnone, C., Hernando, E., Cuevas, J. C., Godoy Herz, M. A., De Petris-Chauvin, A., Simpson, C. G., Brown, J. W. S., Cerdán, P. D., Borevitz, J. O., Mas, P., Ceriani, M. F., Kornblihtt, A. R. & Yanovsky, M. J. A methyl transferase links the circadian clock to the regulation of transcription and alternative splicing. Nature 468, 112-116 (2010).

– Muñoz, M.J., de la Mata, M. & Kornblihtt, A. R. The carboxy terminal domain of RNA polymerase II and alternative splicing. Trends Biochem. Sci. 35, 497-504 (2010).

– Luco, R., Alló, M., Schor, I. E., Kornblihtt, A. R. & Misteli, T. Epigenetics in pre-mRNA splicing. Cell 144, 16-26 (2011).

– Kornblihtt, A. R., Schor, I. E., Alló, M., Dujardin, G., Petrillo, E. & Muñoz, M. Alternative splicing: a pivotal step between eukaryotic transcription and translation. Nat. Rev. Mol. Cell Biol. 14, 153-165 (2013).

– Schor*, I. E., Fiszbein*, A., Petrillo, E. & Kornblihtt, A. R. Intragenic epigenetic changes modulate NCAM alternative splicing upon neuronal differentiation. EMBO J. 32, 2264-2274 (2013).

– Petrillo, E., Godoy Herz, M. A., Simpson, C., Fuller, J., Yanovsky, M. J., Fuchs, A., Brown, J. W. S., Barta, A., Kalyna, M. & Kornblihtt, A. R. A chloroplast retrograde signal regulates nuclear alternative splicing. Science 344, 427-430 (2014).

– Dujardin, G., Lafaille, C., de la Mata, M., Marasco, L., Muñoz, M. J., Le Jossic-Corcos, C., Corcos, L. & Kornblihtt, A. R. How slow RNA Polymerase II elongation favors alternative exon skipping. Molecular Cell 54, 683-690 (2014).

– Alló*, M., Agirre*, E., Bessonov*, S., Bertucci*, P., Gómez Acuña*, L., Buggiano, V., Bellora, N., Singh, B., Petrillo, E., Blaustein, M., Miñana, B., Dujardin, G., Pozzi, B., Pelisch, F., Bechara, E., Agafonov, D. E., Srebrow, A., Lührmann, R., Valcárcel, J., Eyras, E.* & Kornblihtt, A. R.* Argonaute-1 binds transcriptional enhancers and controls constitutive and alternative splicing in human cells. Proc. Natl. Acad. Sci. USA. 111, 15622-15629 (2014).

– Naftelberg, S., Schor, I. E., Ast, G. & Kornblihtt, A. R. Regulation of alternative splicing through coupling with transcription and chromatin structure. Annual Review of Biochemistry 84, 165-198 (2015).

– Fiszbein, A., Giono, L.E., Quaglino, A., Berardino, B. G., Singaut, L., von Bildering, C., Schor, I. E., Pietrasanta, L., Caramelo, J., Srebrow, A. & Kornblihtt, A. R. Alternative splicing of G9a regulates neuronal differentiation. Cell Reports 14, 2797–2808 (2016). Cover of the issue.

– Muñoz*, M. J., Nieto Moreno*, N., Giono*, L. E., Cambindo Botto, A. E., Dujardin, G., Bastianello, G., Lavore, S., Torres-Méndez, A., Menck, C. F. M., Blencowe, B., Irimia, M., Foiani, M. & Kornblihtt, A. R. Major roles of cyclobutane pyrimidine dimers, nucleotide excision repair and ATR in the alternative splicing response to UV irradiation. Cell Reports 12, 2868-2879 (2017). Cover of the issue.

– Godoy Herz, M. A., Kubaczka, M. G., Brzyżek, G., Servi, L., Krzysztoń, M., Simpson, C., Brown, J., Swiezewski, S., Petrillo, E. & Kornblihtt, A. R. Light regulates plant alternative splicing through the control of transcriptional elongation. Molecular Cell 73, 1066-1074 (2019). Featured article. Cover of the issue.

– Maslon, M. M., Braunschweig, U., Aitken, S., Mann, A. R., Kilanowski, F., Hunter, C. J., Blencowe, B. J., Kornblihtt, A. R., Adams, I. R. & Cáceres, J. F. A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes. EMBO J. 38, e101244 (2019).