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 pr...

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Published inCell research Vol. 26; no. 3; pp. 320 - 335
Main Authors Portnoy, Victoria, Lin, Szu Hua Sharon, Li, Kathy H, Burlingame, Alma, Hu, Zheng-Hui, Li, Hao, Li, Long-Cheng
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.03.2016
Nature Publishing Group
Subjects
631/337/572
631/45/500
631/80/86
Argonaute Proteins - metabolism
Biomedical and Life Sciences
Biotinylation
Cell Biology
Cell Line, Tumor
Chromatin - metabolism
Cyclin-Dependent Kinase Inhibitor p21 - genetics
DEAD-box RNA Helicases - metabolism
Histones - metabolism
Humans
Life Sciences
Neoplasm Proteins - metabolism
Nuclear Proteins - metabolism
Original
original-article
Phosphoproteins - metabolism
Promoter Regions, Genetic
RNA - metabolism
RNA Polymerase II - metabolism
RNA, Small Untranslated - metabolism
RNA聚合酶
Transcription Elongation, Genetic
Transcription Factors
Transcription Initiation, Genetic
Transcriptional Activation
Ubiquitination
分子机制
启动子
基因表达
塔
引导
转录水平
转录激活
RITA
transcription
RNAP II
Ago2
saRNA
Argonaute
RNAa
promoter
promoter-targeted RNA
Online AccessGet full text
ISSN1001-0602
1748-7838
DOI10.1038/cr.2016.22

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Summary: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 PAFI 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.
Bibliography:RNAa; promoter; transcription; RNAP II; Argonaute; Ago2; saRNA; promoter-targeted RNA; RITA
31-1568
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 PAFI 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.
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These two authors contributed equally to this work.
ISSN:1001-0602
1748-7838
DOI:10.1038/cr.2016.22