saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:26 |
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| Enthalten in: |
Cell research - 26(2016), 3 vom: 01. März, Seite 320-35 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Portnoy, Victoria [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.12.2016 Date Revised 10.12.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/cr.2016.22 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM257720219 |
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| 100 | 1 | |a Portnoy, Victoria |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription |
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| 500 | |a Date Revised 10.12.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 7 | |a AGO2 protein, human |2 NLM | |
| 650 | 7 | |a Argonaute Proteins |2 NLM | |
| 650 | 7 | |a CDKN1A protein, human |2 NLM | |
| 650 | 7 | |a CTR9 protein, human |2 NLM | |
| 650 | 7 | |a Chromatin |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase Inhibitor p21 |2 NLM | |
| 650 | 7 | |a Histones |2 NLM | |
| 650 | 7 | |a Neoplasm Proteins |2 NLM | |
| 650 | 7 | |a Nuclear Proteins |2 NLM | |
| 650 | 7 | |a Phosphoproteins |2 NLM | |
| 650 | 7 | |a RNA, Small Untranslated |2 NLM | |
| 650 | 7 | |a Transcription Factors |2 NLM | |
| 650 | 7 | |a RNA |2 NLM | |
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| 700 | 1 | |a Lin, Szu Hua Sharon |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Kathy H |e verfasserin |4 aut | |
| 700 | 1 | |a Burlingame, Alma |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Zheng-Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Long-Cheng |e verfasserin |4 aut | |
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