Abstract:
:We investigated whether a continuous transcript is necessary for co-transcriptional pre-mRNA processing. Cutting an intron with the fast-cleaving hepatitis delta ribozyme, but not the slower hammerhead, inhibited splicing. Therefore, exon tethering to RNA polymerase II (Pol II) cannot rescue splicing of a transcript severed by a ribozyme that cleaves rapidly relative to the rate of splicing. Ribozyme cutting also released cap-binding complex (CBC) from the gene, suggesting that exon 1 is not tethered. Unexpectedly, cutting within exons inhibited splicing of distal introns, where exon definition is not affected, probably owing to disruption of the interactions with the CBC and the Pol II C-terminal domain that facilitate splicing. Ribozyme cutting within the mRNA also inhibited 3' processing and transcription termination. We propose that damaging the nascent transcript aborts pre-mRNA processing and that this mechanism may help to prevent association of processing factors with Pol II that is not productively engaged in transcription.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Fong N,Ohman M,Bentley DLdoi
10.1038/nsmb.1652subject
Has Abstractpub_date
2009-09-01 00:00:00pages
916-22issue
9eissn
1545-9993issn
1545-9985pii
nsmb.1652journal_volume
16pub_type
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