Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development
During postnatal development the heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). Here we perform deep RNA-sequencing on RNA from cardiomyocytes and cardiac fibroblasts to conduct a hig...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
2015
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| Online Access: | http://hdl.handle.net/1721.1/96259 |
| _version_ | 1811080676697440256 |
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| author | Giudice, Jimena Xia, Zheng Scavuzzo, Marissa A. Ward, Amanda J. Kalsotra, Auinash Wang, Wei Wehrens, Xander H. T. Cooper, Thomas A. Burge, Christopher B Wang, Eric T Li, Wei |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Giudice, Jimena Xia, Zheng Scavuzzo, Marissa A. Ward, Amanda J. Kalsotra, Auinash Wang, Wei Wehrens, Xander H. T. Cooper, Thomas A. Burge, Christopher B Wang, Eric T Li, Wei |
| author_sort | Giudice, Jimena |
| collection | MIT |
| description | During postnatal development the heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). Here we perform deep RNA-sequencing on RNA from cardiomyocytes and cardiac fibroblasts to conduct a high-resolution analysis of transcriptome changes during postnatal mouse heart development. We reveal extensive changes in gene expression and AS that occur primarily between postnatal days 1 and 28. Cardiomyocytes and cardiac fibroblasts show reciprocal regulation of gene expression reflecting differences in proliferative capacity, cell adhesion functions and mitochondrial metabolism. We further demonstrate that AS plays a role in vesicular trafficking and membrane organization. These AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated changes in expression. Vesicular trafficking genes affected by AS during normal development (when Celf1 is downregulated) show a reversion to neonatal splicing patterns after Celf1 re-expression in adults. Short-term Celf1 induction in adult animals results in disrupted transverse tubule organization and calcium handling. These results identify potential roles for AS in multiple aspects of postnatal heart maturation, including vesicular trafficking and intracellular membrane dynamics. |
| first_indexed | 2024-09-23T11:35:00Z |
| format | Article |
| id | mit-1721.1/96259 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:35:00Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | mit-1721.1/962592022-10-01T04:34:17Z Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development Giudice, Jimena Xia, Zheng Scavuzzo, Marissa A. Ward, Amanda J. Kalsotra, Auinash Wang, Wei Wehrens, Xander H. T. Cooper, Thomas A. Burge, Christopher B Wang, Eric T Li, Wei Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Wang, Eric Tzy-shi Burge, Christopher B. During postnatal development the heart undergoes a rapid and dramatic transition to adult function through transcriptional and post-transcriptional mechanisms, including alternative splicing (AS). Here we perform deep RNA-sequencing on RNA from cardiomyocytes and cardiac fibroblasts to conduct a high-resolution analysis of transcriptome changes during postnatal mouse heart development. We reveal extensive changes in gene expression and AS that occur primarily between postnatal days 1 and 28. Cardiomyocytes and cardiac fibroblasts show reciprocal regulation of gene expression reflecting differences in proliferative capacity, cell adhesion functions and mitochondrial metabolism. We further demonstrate that AS plays a role in vesicular trafficking and membrane organization. These AS transitions are enriched among targets of two RNA-binding proteins, Celf1 and Mbnl1, which undergo developmentally regulated changes in expression. Vesicular trafficking genes affected by AS during normal development (when Celf1 is downregulated) show a reversion to neonatal splicing patterns after Celf1 re-expression in adults. Short-term Celf1 induction in adult animals results in disrupted transverse tubule organization and calcium handling. These results identify potential roles for AS in multiple aspects of postnatal heart maturation, including vesicular trafficking and intracellular membrane dynamics. Myotonic Dystrophy Foundation (Postdoctoral Fellowship) 2015-03-30T18:35:41Z 2015-03-30T18:35:41Z 2014-04 Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/96259 Giudice, Jimena, Zheng Xia, Eric T. Wang, Marissa A. Scavuzzo, Amanda J. Ward, Auinash Kalsotra, Wei Wang, et al. “Alternative Splicing Regulates Vesicular Trafficking Genes in Cardiomyocytes During Postnatal Heart Development.” Nature Communications 5 (April 22, 2014). en_US http://dx.doi.org/10.1038/ncomms4603 Nature Communications Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf PMC |
| spellingShingle | Giudice, Jimena Xia, Zheng Scavuzzo, Marissa A. Ward, Amanda J. Kalsotra, Auinash Wang, Wei Wehrens, Xander H. T. Cooper, Thomas A. Burge, Christopher B Wang, Eric T Li, Wei Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title | Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title_full | Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title_fullStr | Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title_full_unstemmed | Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title_short | Alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| title_sort | alternative splicing regulates vesicular trafficking genes in cardiomyocytes during postnatal heart development |
| url | http://hdl.handle.net/1721.1/96259 |
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