Alternative pre-mRNA splicing
of ion channels

Executive Summary

This collaboration investigates how the read-out of genetic information is modulated by alternative splicing through primate-specific genetic elements and cellular activity. Bioinformatics, genetics, molecular biology and electrophysiology experts will jointly explore the reciprocal relationship between alternative splicing and cellular activity as it is influenced by mutations and mobile genetic elements. By alternative splicing, mammalian organisms generate a complex and highly plastic expression pattern of ion channels that underlies membrane functioning in epithelial and nerve cells. In the nervous system, this mechanism contributes to the physiological adaptation of motor coordination and higher cognitive functions. Failure of cellular systems to appropriately adapt alternative splicing patterns to modified stimuli may either result in disease or aggravate pathological phenotypes.

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Gil Ast
Cord-Michael Becker

Batsheva Kerem
Arthur Konnerth
Hermona Soreq
Stefan Stamm

Work Packages

WP1: Generation of new alternative exons through mobile genetic elements

WP2: Allelic variations that govern alternative splicing of the CFTR ion channel

WP3: Regulation of splice site selection by Ca++ concentration-dependent phosphorylation of splicing factors

WP4: Mobile genetic elements causing hypertonic motor disorders through missplicing of ion channels

WP5: Control of calcium-dependent gene expression through receptor tyrosine kinase TrkB isoforms

WP6: Alternative splicing modulations under imbalanced cholinergic signaling: from spliceosome components to target transcripts

Selected Publications

  1. Kishore, S., and Stamm, S. (2006).
    The snoRNA HBII-52 regulates alternative splicing of the serotonin receptor 2C
    Science 311, 230-232. (Epub 2005 Dec 15.)

  2. Meshorer, E., Biton, I., Ben-Shaul, Y., Ben-Ari, S., Assaf, Y., Soreq, H. and Cohen, Y. (2005).
    Chronic cholinergic imbalances promote brain diffusion and transport abnormalities
    FASEB J., 19, 910-922

  3. Pick, M., Perry, C., Grisaru, D., Lapidot, Z., Naparstek, E., Deutsch, V. and Soreq, H. (2005).
    Stress-induced cholinergic signaling promotes inflammation-associated thrombopoiesis
    Blood, 2006 Apr 15;107(8):3397-406. Epub 2005 Dec 27

  4. Magen A, Ast G. (2005)
    The importance of being divisible by three in alternative splicing
    Nucleic Acids Research (2005)Vol. 33,No. 17: 5574.5582

  5. Kol G, Lev-Maor G, Ast G. (2005)
    Human-Mouse Comparative Analysis reveals that Branch-site plasticity contributes to splicing regulation
    Human Molecular Genetics (2005) 14: 1559-1568

Prof. Dr. Batsheva Kerem
Prof. Dr. Stefan Stamm