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

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.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Listerman I,Sapra AK,Neugebauer KM

doi

10.1038/nsmb1135

subject

Has Abstract

pub_date

2006-09-01 00:00:00

pages

815-22

issue

9

eissn

1545-9993

issn

1545-9985

pii

nsmb1135

journal_volume

13

pub_type

杂志文章

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