Journal
JOURNAL OF CELL BIOLOGY
Volume 193, Issue 5, Pages 819-829Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201009012
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Funding
- Sidaction, Agence Nationale de Recherche sur le Sida
- EC RiboSys [LSHG-CT-2005-518280]
- EURASNET
- Centre for Systems Biology at Edinburgh
- Biotechnology and Biological Sciences Research Council
- Engineering and Physical Sciences Research Council [BB/D019621/1]
- Wellcome Trust
- EMBO [171-2006]
- Deutsche Forschungsgemeinschaft [Schm 2659/1-1]
- BBSRC [BB/D019621/1] Funding Source: UKRI
- Grants-in-Aid for Scientific Research [21228003] Funding Source: KAKEN
- Biotechnology and Biological Sciences Research Council [BB/D019621/1] Funding Source: researchfish
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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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