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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Main Authors: Lior Faigenbloom, Nimrod D Rubinstein, Yoel Kloog, Itay Mayrose, Tal Pupko, Reuven Stein
Format: Article
Language:English
Published: Springer Nature 2015-12-01
Series:Molecular Systems Biology
Subjects:
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.
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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
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AT yoelkloog regulationofalternativesplicingatthesinglecelllevel
AT itaymayrose regulationofalternativesplicingatthesinglecelllevel
AT talpupko regulationofalternativesplicingatthesinglecelllevel
AT reuvenstein regulationofalternativesplicingatthesinglecelllevel