saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription
| Autor: | Hao Li, Alma L. Burlingame, Szu Hua Sharon Lin, Zheng-Hui Hu, Long-Cheng Li, Kathy H. Li, Victoria Portnoy |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cyclin-Dependent Kinase Inhibitor p21 Transcriptional Activation Transcription Elongation Genetic Ago2 RNA activation RNA polymerase II Biology DEAD-box RNA Helicases Histones 03 medical and health sciences promoter-targeted RNA Transcription (biology) Cell Line Tumor RITA Humans Biotinylation Promoter Regions Genetic Molecular Biology Transcription factor Transcription Initiation Genetic Genetics promoter Ubiquitination Nuclear Proteins Promoter Cell Biology Argonaute Phosphoproteins Chromatin Cell biology Neoplasm Proteins RNAP II 030104 developmental biology Argonaute Proteins biology.protein RNA RNA Small Untranslated Original Article RNA Polymerase II transcription saRNA RNAa Transcription Factors |
| Zdroj: | Cell Research |
| ISSN: | 1748-7838 |
| Popis: | Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process. |
| Databáze: | OpenAIRE |
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