Control of alternative splicing through siRNA-mediated transcriptional gene silencing
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...
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2009
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15459993_v16_n7_p717_Allo http://hdl.handle.net/20.500.12110/paper_15459993_v16_n7_p717_Allo |
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paper:paper_15459993_v16_n7_p717_Allo2025-07-30T18:56:54Z Control of alternative splicing through siRNA-mediated transcriptional gene silencing argonaute 1 protein heterochromatin protein 1 heterochromatin protein 1alpha histone H3 lysine RNA polymerase II small interfering RNA unclassified drug alternative RNA splicing article cell specificity controlled study exon gene expression regulation gene silencing HeLa cell heterochromatin human human cell intron liver cell carcinoma methylation priority journal promoter region regulatory mechanism transcription regulation 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 HP1α and the reduction in RNA polymerase II processivity suggest a mechanism involving the kinetic coupling of transcription and alternative splicing. © 2009 Nature America, Inc. All rights reserved. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15459993_v16_n7_p717_Allo http://hdl.handle.net/20.500.12110/paper_15459993_v16_n7_p717_Allo |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
argonaute 1 protein heterochromatin protein 1 heterochromatin protein 1alpha histone H3 lysine RNA polymerase II small interfering RNA unclassified drug alternative RNA splicing article cell specificity controlled study exon gene expression regulation gene silencing HeLa cell heterochromatin human human cell intron liver cell carcinoma methylation priority journal promoter region regulatory mechanism transcription regulation |
| spellingShingle |
argonaute 1 protein heterochromatin protein 1 heterochromatin protein 1alpha histone H3 lysine RNA polymerase II small interfering RNA unclassified drug alternative RNA splicing article cell specificity controlled study exon gene expression regulation gene silencing HeLa cell heterochromatin human human cell intron liver cell carcinoma methylation priority journal promoter region regulatory mechanism transcription regulation Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| topic_facet |
argonaute 1 protein heterochromatin protein 1 heterochromatin protein 1alpha histone H3 lysine RNA polymerase II small interfering RNA unclassified drug alternative RNA splicing article cell specificity controlled study exon gene expression regulation gene silencing HeLa cell heterochromatin human human cell intron liver cell carcinoma methylation priority journal promoter region regulatory mechanism transcription regulation |
| description |
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 HP1α and the reduction in RNA polymerase II processivity suggest a mechanism involving the kinetic coupling of transcription and alternative splicing. © 2009 Nature America, Inc. All rights reserved. |
| title |
Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| title_short |
Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| title_full |
Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| title_fullStr |
Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| title_full_unstemmed |
Control of alternative splicing through siRNA-mediated transcriptional gene silencing |
| title_sort |
control of alternative splicing through sirna-mediated transcriptional gene silencing |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15459993_v16_n7_p717_Allo http://hdl.handle.net/20.500.12110/paper_15459993_v16_n7_p717_Allo |
| _version_ |
1840320860252012544 |