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Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons
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 re...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132704/ https://www.ncbi.nlm.nih.gov/pubmed/25030907 http://dx.doi.org/10.1093/nar/gku532 |
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author | Szafranski, Karol Fritsch, Claudia Schumann, Frank Siebel, Lisa Sinha, Rileen Hampe, Jochen Hiller, Michael Englert, Christoph Huse, Klaus Platzer, Matthias |
author_facet | Szafranski, Karol Fritsch, Claudia Schumann, Frank Siebel, Lisa Sinha, Rileen Hampe, Jochen Hiller, Michael Englert, Christoph Huse, Klaus Platzer, Matthias |
author_sort | Szafranski, Karol |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4132704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41327042014-12-01 Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons Szafranski, Karol Fritsch, Claudia Schumann, Frank Siebel, Lisa Sinha, Rileen Hampe, Jochen Hiller, Michael Englert, Christoph Huse, Klaus Platzer, Matthias Nucleic Acids Res Gene regulation, Chromatin and Epigenetics 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. Oxford University Press 2014-08-18 2014-07-16 /pmc/articles/PMC4132704/ /pubmed/25030907 http://dx.doi.org/10.1093/nar/gku532 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Gene regulation, Chromatin and Epigenetics Szafranski, Karol Fritsch, Claudia Schumann, Frank Siebel, Lisa Sinha, Rileen Hampe, Jochen Hiller, Michael Englert, Christoph Huse, Klaus Platzer, Matthias Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title | Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title_full | Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title_fullStr | Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title_full_unstemmed | Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title_short | Physiological state co-regulates thousands of mammalian mRNA splicing events at tandem splice sites and alternative exons |
title_sort | physiological state co-regulates thousands of mammalian mrna splicing events at tandem splice sites and alternative exons |
topic | Gene regulation, Chromatin and Epigenetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4132704/ https://www.ncbi.nlm.nih.gov/pubmed/25030907 http://dx.doi.org/10.1093/nar/gku532 |
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