Gil Ast

Research Focus

The long term objectives of our lab are to understand how alternative splicing create primate-specific genomic diversity; how alternative splicing and the birthing process of new exons in the human genome are linked to genetic disorders and cancer; and what are the evolutionary process that create alternative splicing, and whether this process responsible for higher order of phenotypic complexity.

Our research combines bioinformatics and molecular biology tools to uncover the following aims: (1) How many primate-specific exons we have in the human genome and which contribute to some of the unique features of humans. (2) Whether formation of new exons due to somatic mutations involve in cancer. (3) What are the evolutionary forces that shape the human transcriptome? (4) What is the evolution of alternative splicing?

Publications

  1. Llorian, M., Schwartz, S., Clark, T.A., Hollander, D., Tan, L-Y., Spellman, R., Gordon, A., Schweitzer, A.C., de la Grange, P., Ast, G., Smith, C.W.J. (2010). Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB. Nature Structural & Molecular Biology, [Epub ahead of print].
  2. Schwartz, S.H., Silva, J., Burstein, D., Pupko, T., Eyras, E., Ast, G. (2008). Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes. Genome Research 18(1), 88-103.
  3. Kim, E., Goren, A. and Ast, G. (2008). Alternative splicing and disease. RNA Biology 2008 Mar 22;5(1). [epub ahead of print]
  4. Ram, O., Schwartz, S. and Ast. G. (2008). Multifactorial interplay controls the splicing profile of Alu derived exons. Molecular and Cellular Biology 2008 Mar 10. [epub ahead of print]
  5. Gal-Mark, N., Schwartz, S. and Ast, G. (2008). Alternative splicing of Alu exons--two arms are better than one. Nucleic Acids Research 2008 Feb 14.
  6. Goren, A., Kim, E., Amit, M., Bochner, R., Lev-Maor, G., Ahituv, N. and Ast, G. (2008). Alternative approach to a heavy weight problem. Genome Research 2008 Feb.
  7. Kim, E., Goren, A. and Ast, G. (2008). Alternative splicing: current perspectives. Bioessays 30(1), 38-47.
  8. Kim, E., Goren, A. and Ast, G. (2008). Insights into the connection between cancer and alternative splicing. Trends in Genetics 2008 Jan.
  9. Amit, M., Sela, N., Keren, H., Melamed, Z., Muler, I., Shomron, N., Izraeli, S. and Ast, G. (2007). Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene. BMC Molecular Biology 8, 109.
  10. Schwartz, S., Silva, J., Burstein, D., Pupko, T., Eyras, E., and Ast, G. (2007). Large-scale comparative analysis of splicing signals and their corresponding splicing factors in eukaryotes. Genome Research 18, 88-103.
  11. Lev-Maor, G., Goren, A., Sela, N., Kim, E., Keren, H., Doron-Faigenboim, A., Leibman-Barak, S., Pupko, T., Ast, G. (2007). The "Alternative" Choice of Constitutive Exons throughout Evolution. PLoS Genetics 3(11), e203.
  12. Mersch, B., Sela, N., Ast, G., Suhai, S., Hotz-Wagenblatt, A. (2007). SERpredict: Detection of tissue- or tumor-specific isoforms generated through exonization of transposable elements. BMC Genetics 8(1), 78.
  13. Levy, A., Sela, N. and Ast, G. (2007). TranspoGene and microTranspoGene: transposed elements influence on the transcriptome of seven vertebrates and invertebrates. Nucleic Acids Research 36, D47–D52.
  14. Alberstein, M., Amit, M., Vaknin, K., O'Donnell, A., Farhy, C., Lerenthal, Y., Shomron, N., Shaham, O., Sharrocks, A.D., Ashery-Padan, R., and Ast, G. (2007). Regulation of transcription of the RNA splicing factor hSlu7 by Elk-1 and Sp1 affects alternative splicing. RNA 13, 1988 - 1999.
  15. Sela, N., Mersch, B., Gal-Mark, N., Lev-Maor, G., Hotz-Wagenblatt, A. and Ast, G. (2007). Comparative analysis of transposed element insertion within human and mouse genomes reveals Alu's unique role in shaping the human transcriptome. Genome Biology 8(6), R127.
  16. Cheishvili, D., Maayan, C., Smith, Y., Ast, G., and Razin,. A. (2007). IKAP/hELP1 deficiency in the cerebrum of familial dysautonomia patients results in down regulation of genes involved in oligodendrocyte differentiation and in myelination. Human Molecular Genetics 16(17), 2097-2104.
  17. Koren, E., Lev-Maor, G., and Ast, G. (2007). The emergence of alternative 3' and 5' splice site exons from constitutive exons. PLoS Computational Biology 3(5), e95.
  18. Lev-Maor, G., Sorek, R., Levanon, E.Y., Paz, N., Eisenberg, E. and Ast, G. (2007). RNA-editing-mediated exon evolution. Genome Biology 8(2), R29.
  19. Kim, E., Magen, A., Ast, G. (2007). Different levels of alternative splicing among eukaryotes. Nucleic Acids Research 35(1), 125-31.
  20. Ram, O., Ast, G. (2007). SR proteins: a foot on the exon before the transition from intron to exon definition. Trends in Genetics 23(1), 5-7.
  21. Kol, G., Lev-Maor, G., Ast, G. (2005). Human-Mouse Comparative Analysis reveals that Branch-site plasticity contributes to splicing regulation. Human Molecular Genetics. 14, 1559-1568.
  22. Shomron, N., Alberstein, M., Reznik M. and Ast, G. (2005). Stress alters the subcellular distribution of hSlu7 and modulates alternative splicing. Journal of Cell Science 118, 1151-1159.
  23. Sorek, R., Lev-Maor, G., Reznik, M., Dagan, T., Belinky, F., Graur, D., Ast, G. (2004). Minimal conditions for exonization of intronic sequences: 5’ splice site formation in Alu exons. Molecular Cell 14(2), 221-231.
  24. Ast, G. (2004). How did alternative splicing evolve? Nature Reviews Genetics 5(10), 773-782.
  25. Lev-Maor, G., Sorek, R., Shomron, N., Ast, G. (2003). The birth of an alternatively spliced exon: 3' splice-site selection in Alu exons. Science 300, 1288-1291.

Key lab techniques: Comparative genomics, in vivo minigene analysis, datasets of homologous exons and introns

Lab contact: gilast@post.tau.ac.il

Lab website: http://www.tau.ac.il/~gilast/