Abstract:
:When targeting promoter regions, small interfering RNAs (siRNAs) trigger a previously proposed pathway known as transcriptional gene silencing by promoting heterochromatin formation. Here we show that siRNAs targeting intronic or exonic sequences close to an alternative exon regulate the splicing of that exon. The effect occurred in hepatoma and HeLa cells with siRNA antisense strands designed to enter the silencing pathway, suggesting hybridization with nascent pre-mRNA. Unexpectedly, in HeLa cells the sense strands were also effective, suggesting that an endogenous antisense transcript, detectable in HeLa but not in hepatoma cells, acts as a target. The effect depends on Argonaute-1 and is counterbalanced by factors favoring chromatin opening or transcriptional elongation. The increase in heterochromatin marks (dimethylation at Lys9 and trimethylation at Lys27 of histone H3) at the target site, the need for the heterochromatin-associated protein HP1alpha and the reduction in RNA polymerase II processivity suggest a mechanism involving the kinetic coupling of transcription and alternative splicing.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Alló M,Buggiano V,Fededa JP,Petrillo E,Schor I,de la Mata M,Agirre E,Plass M,Eyras E,Elela SA,Klinck R,Chabot B,Kornblihtt ARdoi
10.1038/nsmb.1620subject
Has Abstractpub_date
2009-07-01 00:00:00pages
717-24issue
7eissn
1545-9993issn
1545-9985pii
nsmb.1620journal_volume
16pub_type
杂志文章abstract::Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Di...
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abstract:: ...
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