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

Research output: Contribution to journalArticle

  • Ute Schmidt
  • E Basyuk
  • Marie-Cécile Robert
  • M. Yoshida
  • J-P Villemin
  • D Auboeuf
  • Stuart Aitken
  • Edouard Bertrand

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http://jcb.rupress.org/content/193/5/819
Original languageEnglish
Pages (from-to)819-829
Number of pages11
JournalJournal of Cell Biology
Volume193
Issue number5
DOIs
Publication statusPublished - 2011

Abstract

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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