Regulation of alternative splicing at the single‐cell level
Abstract Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among...
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| Format: | Article |
| Language: | English |
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Springer Nature
2015-12-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20156278 |
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| author | Lior Faigenbloom Nimrod D Rubinstein Yoel Kloog Itay Mayrose Tal Pupko Reuven Stein |
| author_facet | Lior Faigenbloom Nimrod D Rubinstein Yoel Kloog Itay Mayrose Tal Pupko Reuven Stein |
| author_sort | Lior Faigenbloom |
| collection | DOAJ |
| description | Abstract Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among individual cells is governed is poorly understood. Using single‐cell gene expression, we show that the precision of inclusion levels of alternative exons is determined by the degree of evolutionary conservation at their flanking intronic regions. Moreover, the inclusion levels of alternative exons, as well as the expression levels of the transcripts harboring them, also contribute to this precision. We further show that alternative exons whose inclusion levels are considerably changed during stem cell differentiation are also subject to this regulation. Our results imply that alternative splicing is coordinately regulated to achieve accuracy in relative isoform abundances and that such accuracy may be important in determining cell fate. |
| format | Article |
| id | doaj-art-a1c194120e6f41bcaba977fca767eee0 |
| institution | OA Journals |
| issn | 1744-4292 |
| language | English |
| publishDate | 2015-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-a1c194120e6f41bcaba977fca767eee02025-08-20T02:12:03ZengSpringer NatureMolecular Systems Biology1744-42922015-12-01111211210.15252/msb.20156278Regulation of alternative splicing at the single‐cell levelLior Faigenbloom0Nimrod D Rubinstein1Yoel Kloog2Itay Mayrose3Tal Pupko4Reuven Stein5The Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv UniversityDepartment of Molecular and Cellular Biology, Harvard UniversityThe Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv UniversityThe Department of Molecular Biology and Ecology of Plants, George S. Wise Faculty of Life Sciences, Tel Aviv UniversityThe Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv UniversityThe Department of Neurobiology, George S. Wise Faculty of Life Sciences, Tel Aviv UniversityAbstract Alternative splicing is a key cellular mechanism for generating distinct isoforms, whose relative abundances regulate critical cellular processes. It is therefore essential that inclusion levels of alternative exons be tightly regulated. However, how the precision of inclusion levels among individual cells is governed is poorly understood. Using single‐cell gene expression, we show that the precision of inclusion levels of alternative exons is determined by the degree of evolutionary conservation at their flanking intronic regions. Moreover, the inclusion levels of alternative exons, as well as the expression levels of the transcripts harboring them, also contribute to this precision. We further show that alternative exons whose inclusion levels are considerably changed during stem cell differentiation are also subject to this regulation. Our results imply that alternative splicing is coordinately regulated to achieve accuracy in relative isoform abundances and that such accuracy may be important in determining cell fate.https://doi.org/10.15252/msb.20156278alternative splicingevolutionary conservationinclusion levelsingle cellsplicing regulation |
| spellingShingle | Lior Faigenbloom Nimrod D Rubinstein Yoel Kloog Itay Mayrose Tal Pupko Reuven Stein Regulation of alternative splicing at the single‐cell level Molecular Systems Biology alternative splicing evolutionary conservation inclusion level single cell splicing regulation |
| title | Regulation of alternative splicing at the single‐cell level |
| title_full | Regulation of alternative splicing at the single‐cell level |
| title_fullStr | Regulation of alternative splicing at the single‐cell level |
| title_full_unstemmed | Regulation of alternative splicing at the single‐cell level |
| title_short | Regulation of alternative splicing at the single‐cell level |
| title_sort | regulation of alternative splicing at the single cell level |
| topic | alternative splicing evolutionary conservation inclusion level single cell splicing regulation |
| url | https://doi.org/10.15252/msb.20156278 |
| work_keys_str_mv | AT liorfaigenbloom regulationofalternativesplicingatthesinglecelllevel AT nimroddrubinstein regulationofalternativesplicingatthesinglecelllevel AT yoelkloog regulationofalternativesplicingatthesinglecelllevel AT itaymayrose regulationofalternativesplicingatthesinglecelllevel AT talpupko regulationofalternativesplicingatthesinglecelllevel AT reuvenstein regulationofalternativesplicingatthesinglecelllevel |