A splicing-dependent transcriptional checkpoint associated with prespliceosome formation

Keerthi T Chathoth, J David Barrass, Shaun Webb, Jean D Beggs

Research output: Contribution to journalArticlepeer-review


There is good evidence for functional interactions between splicing and transcription in eukaryotes, but how and why these processes are coupled remain unknown. Prp5 protein (Prp5p) is an RNA-stimulated adenosine triphosphatase (ATPase) required for prespliceosome formation in yeast. We demonstrate through in vivo RNA labeling that, in addition to a splicing defect, the prp5-1 mutation causes a defect in the transcription of intron-containing genes. We present chromatin immunoprecipitation evidence for a transcriptional elongation defect in which RNA polymerase that is phosphorylated at Ser5 of the largest subunit's heptad repeat accumulates over introns and that this defect requires Cus2 protein. A similar accumulation of polymerase was observed when prespliceosome formation was blocked by a mutation in U2 snRNA. These results indicate the existence of a transcriptional elongation checkpoint that is associated with prespliceosome formation during cotranscriptional spliceosome assembly. We propose a role for Cus2p as a potential checkpoint factor in transcription.
Original languageEnglish
Pages (from-to)779-790
Number of pages12
JournalMolecular Cell
Issue number5
Early online date20 Feb 2014
Publication statusPublished - 6 Mar 2014


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