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  Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells

Listerman, I., Sapra, A. K., & Neugebauer, K. M. (2006). Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells. Nature Structure and Molecular Biology, 13(9), 815-822.

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 Creators:
Listerman, Imke1, Author           
Sapra, Aparna K, Author
Neugebauer, Karla M1, Author           
Affiliations:
1Max Planck Institute of Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: Coupling between transcription and RNA processing is a key gene regulatory mechanism. Here we use chromatin immunoprecipitation to detect transcription-dependent accumulation of the precursor mRNA (pre-mRNA) splicing factors hnRNP A1, U2AF65 and U1 and U5 snRNPs on the intron-containing human FOS gene. These factors were poorly detected on intronless heat-shock and histone genes, a result that opposes direct recruitment by RNA polymerase II (Pol II) or the cap-binding complex in vivo. However, an observed RNA-dependent interaction between U2AF65 and active forms of Pol II may stabilize U2AF65 binding to intron-containing nascent RNA. We establish chromatin-RNA immunoprecipitation and show that FOS pre-mRNA is cotranscriptionally spliced. Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis.

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 Dates: 2006
 Publication Status: Issued
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 Identifiers: eDoc: 311211
Other: 683
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Title: Nature Structure and Molecular Biology
Source Genre: Journal
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Pages: - Volume / Issue: 13 (9) Sequence Number: - Start / End Page: 815 - 822 Identifier: -