Llorian, M;
Gooding, C;
Bellora, N;
Hallegger, M;
Buckroyd, A;
Wang, X;
Rajgor, D;
... Smith, CWJ; + view all
(2016)
The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators.
Nucleic Acids Research
, 44
(18)
pp. 8933-8950.
10.1093/nar/gkw560.
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Abstract
Alternative splicing (AS) is a key component of gene expression programs that drive cellular differentiation. Smooth muscle cells (SMCs) are important in the function of a number of physiological systems; however, investigation of SMC AS has been restricted to a handful of events. We profiled transcriptome changes in mouse de-differentiating SMCs and observed changes in hundreds of AS events. Exons included in differentiated cells were characterized by particularly weak splice sites and by upstream binding sites for Polypyrimidine Tract Binding protein (PTBP1). Consistent with this, knockdown experiments showed that that PTBP1 represses many smooth muscle specific exons. We also observed coordinated splicing changes predicted to downregulate the expression of core components of U1 and U2 snRNPs, splicing regulators and other post-transcriptional factors in differentiated cells. The levels of cognate proteins were lower or similar in differentiated compared to undifferentiated cells. However, levels of snRNAs did not follow the expression of splicing proteins, and in the case of U1 snRNP we saw reciprocal changes in the levels of U1 snRNA and U1 snRNP proteins. Our results suggest that the AS program in differentiated SMCs is orchestrated by the combined influence of auxiliary RNA binding proteins, such as PTBP1, along with altered activity and stoichiometry of the core splicing machinery.
| Type: | Article |
|---|---|
| Title: | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/nar/gkw560 |
| Publisher version: | https://doi.org/10.1093/nar/gkw560 |
| Language: | English |
| Additional information: | © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http: // creativecommons.org / licenses / by / 4.0 / ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Tract Binding-Protein, Messenger-Rna Decay, Core Spliceosomal Machinery, Widespread Intron Retention, Mutually Exclusive Exon, Nonsense-Mediated Decay, Polypyrimidine Tract, Alpha-Actinin, Gene-Expression, Alpha(7)Beta(1) Integrin |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1502783 |
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