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Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation

Splicing is a key process that expands the coding capacity of genomes. Its kinetics remain poorly characterized, and the distribution of splicing time caused by the stochasticity of single splicing events is expected to affect regulation efficiency. We conducted a small-scale survey on 40 introns in...

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Autores principales: Schmidt, Ute, Basyuk, Eugenia, Robert, Marie-Cécile, Yoshida, Minoru, Villemin, Jean-Philippe, Auboeuf, Didier, Aitken, Stuart, Bertrand, Edouard
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105549/
https://www.ncbi.nlm.nih.gov/pubmed/21624952
http://dx.doi.org/10.1083/jcb.201009012
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author Schmidt, Ute
Basyuk, Eugenia
Robert, Marie-Cécile
Yoshida, Minoru
Villemin, Jean-Philippe
Auboeuf, Didier
Aitken, Stuart
Bertrand, Edouard
author_facet Schmidt, Ute
Basyuk, Eugenia
Robert, Marie-Cécile
Yoshida, Minoru
Villemin, Jean-Philippe
Auboeuf, Didier
Aitken, Stuart
Bertrand, Edouard
author_sort Schmidt, Ute
collection PubMed
description Splicing is a key process that expands the coding capacity of genomes. Its kinetics remain poorly characterized, and the distribution of splicing time caused by the stochasticity of single splicing events is expected to affect regulation efficiency. We conducted a small-scale survey on 40 introns in human cells and observed that most were spliced cotranscriptionally. Consequently, we constructed a reporter system that splices cotranscriptionally and can be monitored in live cells and in real time through the use of MS2–GFP. All small nuclear ribonucleoproteins (snRNPs) are loaded on nascent pre-mRNAs, and spliceostatin A inhibits splicing but not snRNP recruitment. Intron removal occurs in minutes and is best described by a model where several successive steps are rate limiting. Each pre-mRNA molecule is predicted to require a similar time to splice, reducing kinetic noise and improving the regulation of alternative splicing. This model is relevant to other kinetically controlled processes acting on few molecules.
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spelling pubmed-31055492011-11-30 Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation Schmidt, Ute Basyuk, Eugenia Robert, Marie-Cécile Yoshida, Minoru Villemin, Jean-Philippe Auboeuf, Didier Aitken, Stuart Bertrand, Edouard J Cell Biol Research Articles Splicing is a key process that expands the coding capacity of genomes. Its kinetics remain poorly characterized, and the distribution of splicing time caused by the stochasticity of single splicing events is expected to affect regulation efficiency. We conducted a small-scale survey on 40 introns in human cells and observed that most were spliced cotranscriptionally. Consequently, we constructed a reporter system that splices cotranscriptionally and can be monitored in live cells and in real time through the use of MS2–GFP. All small nuclear ribonucleoproteins (snRNPs) are loaded on nascent pre-mRNAs, and spliceostatin A inhibits splicing but not snRNP recruitment. Intron removal occurs in minutes and is best described by a model where several successive steps are rate limiting. Each pre-mRNA molecule is predicted to require a similar time to splice, reducing kinetic noise and improving the regulation of alternative splicing. This model is relevant to other kinetically controlled processes acting on few molecules. The Rockefeller University Press 2011-05-30 /pmc/articles/PMC3105549/ /pubmed/21624952 http://dx.doi.org/10.1083/jcb.201009012 Text en © 2011 Schmidt et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Schmidt, Ute
Basyuk, Eugenia
Robert, Marie-Cécile
Yoshida, Minoru
Villemin, Jean-Philippe
Auboeuf, Didier
Aitken, Stuart
Bertrand, Edouard
Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title_full Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title_fullStr Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title_full_unstemmed Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title_short Real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
title_sort real-time imaging of cotranscriptional splicing reveals a kinetic model that reduces noise: implications for alternative splicing regulation
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3105549/
https://www.ncbi.nlm.nih.gov/pubmed/21624952
http://dx.doi.org/10.1083/jcb.201009012
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