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Nucleic Acids Res. 2014 Aug;42(14):8895-904. doi: 10.1093/nar/gku532. Epub 2014 Jul 16.

Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons.

Author information

1
Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany szafrans@fli-leibniz.de.
2
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.
3
Fritz Lipmann Institute-Institute for Age Research, Beutenbergstr. 11, 07745 Jena, Germany.
4
Medical Department I, University Hospital, Technical University Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
5
Max Planck Institute of Molecular Cell Biology and Genetics & Max Planck Institute for the Physics of Complex Systems, Pfotenhauerstr. 108, 01307 Dresden, Germany.

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.

PMID:
25030907
PMCID:
PMC4132704
DOI:
10.1093/nar/gku532
[Indexed for MEDLINE]
Free PMC Article

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