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The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators
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 transc...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062968/ https://www.ncbi.nlm.nih.gov/pubmed/27317697 http://dx.doi.org/10.1093/nar/gkw560 |
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author | Llorian, Miriam Gooding, Clare Bellora, Nicolas Hallegger, Martina Buckroyd, Adrian Wang, Xiao Rajgor, Dipen Kayikci, Melis Feltham, Jack Ule, Jernej Eyras, Eduardo Smith, Christopher W.J. |
author_facet | Llorian, Miriam Gooding, Clare Bellora, Nicolas Hallegger, Martina Buckroyd, Adrian Wang, Xiao Rajgor, Dipen Kayikci, Melis Feltham, Jack Ule, Jernej Eyras, Eduardo Smith, Christopher W.J. |
author_sort | Llorian, Miriam |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5062968 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50629682016-10-14 The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators Llorian, Miriam Gooding, Clare Bellora, Nicolas Hallegger, Martina Buckroyd, Adrian Wang, Xiao Rajgor, Dipen Kayikci, Melis Feltham, Jack Ule, Jernej Eyras, Eduardo Smith, Christopher W.J. Nucleic Acids Res RNA 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. Oxford University Press 2016-10-14 2016-06-17 /pmc/articles/PMC5062968/ /pubmed/27317697 http://dx.doi.org/10.1093/nar/gkw560 Text en © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/4.0/ 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. |
spellingShingle | RNA Llorian, Miriam Gooding, Clare Bellora, Nicolas Hallegger, Martina Buckroyd, Adrian Wang, Xiao Rajgor, Dipen Kayikci, Melis Feltham, Jack Ule, Jernej Eyras, Eduardo Smith, Christopher W.J. The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title_full | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title_fullStr | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title_full_unstemmed | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title_short | The alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
title_sort | alternative splicing program of differentiated smooth muscle cells involves concerted non-productive splicing of post-transcriptional regulators |
topic | RNA |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5062968/ https://www.ncbi.nlm.nih.gov/pubmed/27317697 http://dx.doi.org/10.1093/nar/gkw560 |
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