title: Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons.
abstract: Thousands of tandem alternative splice sites (TASS) give rise to mRNA insertion/deletion variants with small size differences. Recent work has concentrated on the question of biological relevance in general, and the physiological regulation of TASS in particular. We have quantitatively studied 11 representative TASS cases in comparison to one mutually exclusive exon case and two cassette exons (CEs) using a panel of human and mouse tissues, as well as cultured cell lines. Tissues show small but significant differences in TASS isoform ratios, with a variance 4- to 20-fold lower than seen for CEs. Remarkably, in cultured cells, all studied alternative splicing (AS) cases showed a cell-density-dependent shift of isoform ratios with similar time series profiles. A respective genome-wide co-regulation of TASS splicing was shown by next-generation mRNA sequencing data. Moreover, data from human and mouse organs indicate that this co-regulation of TASS occurs in vivo, with brain showing the strongest difference to other organs. Together, the results indicate a physiological AS regulation mechanism that functions almost independently from the splice site context and sequence.
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany szafrans@fli-leibniz.de.
authors.forename: Karol
authors.initials: K
authors.lastname: Szafranski
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany Department of General Internal Medicine, Christian-Albrechts-University, Schittenhelmstrasse 12, 24105 Kiel, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fritsch
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany Department of General Internal Medicine, Christian-Albrechts-University, Schittenhelmstrasse 12, 24105 Kiel, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schumann
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Siebel
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Rileen
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Medical Department I, University Hospital, Technical University Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics & Max Planck Institute for the Physics of Complex Systems, Pfotenhauerstr. 108, 01307 Dresden, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hiller
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Englert
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Huse
authors.affiliation: Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002460:Cell Line; D005091:Exons; D015894:Genome, Human; D006801:Humans; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022821:RNA Splice Sites
chemical_list: D020033:Protein Isoforms; D022821:RNA Splice Sites