INVESTIGADORES
KORNBLIHTT Alberto Rodolfo
artículos
Título:
Control of alternative splicing through siRNA-mediated transcriptional gene silencing.
Autor/es:
ALLÓ MARIANO; BUGGIANO V; FEDEDA JP; PETRILLO E; SCHOR IGNACIO; DE LA MATA M; AGIRRE E; PLASS M; EYRAS E; ELELA S; KLINCK R; CHABOT B; KORNBLIHTT AR.
Revista:
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Editorial:
NATURE PUBLISHING GROUP
Referencias:
Año: 2009 p. 717 - 724
ISSN:
1545-9985
Resumen:
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.