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- W1987865481 abstract "Co-transcriptional splicing of pre-mRNAs has been proposed to involve exon tethering to the elongating RNA polymerase II. By inserting a fast-cleaving ribozyme in the nascent transcript, the linear integrity of the transcript is found to be key to splicing, arguing against tethering and for a pathway that clears such disrupted transcripts. We investigated whether a continuous transcript is necessary for co-transcriptional pre-mRNA processing. Cutting an intron with the fast-cleaving hepatitis δ 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." @default.
- W1987865481 created "2016-06-24" @default.
- W1987865481 creator A5012839003 @default.
- W1987865481 creator A5046864428 @default.
- W1987865481 creator A5058995132 @default.
- W1987865481 date "2009-08-23" @default.
- W1987865481 modified "2023-09-27" @default.
- W1987865481 title "Fast ribozyme cleavage releases transcripts from RNA polymerase II and aborts co-transcriptional pre-mRNA processing" @default.
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- W1987865481 doi "https://doi.org/10.1038/nsmb.1652" @default.
- W1987865481 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2755206" @default.
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- W1987865481 hasPublicationYear "2009" @default.
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