期刊
GENES & DEVELOPMENT
卷 32, 期 11-12, 页码 836-848出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.311688.118
关键词
CHD4/NuRD; heat shock; lncRNA; RNA polymerase I transcription; rRNA genes; DNA-RNA triplexes
资金
- Deutsche Forschungsgemeinschaft [GR475/22-2, SFB1036]
- CellNetworks (EcTop Survey)
- Baden-Wurttemberg Stiftung
Attenuation of pre-rRNA synthesis in response to elevated temperature is accompanied by increased levels of PAPAS (promoter and pre-rRNA antisense), a long noncoding RNA (lncRNA) that is transcribed in an orientation antisense to pre-rRNA. Here we show that PAPAS interacts directly with DNA, forming a DNA-RNA triplex structure that tethers PAPAS to a stretch of purines within the enhancer region, thereby guiding associated CHD4/NuRD (nucleosome remodeling and deacetylation) to the rDNA promoter. Protein-RNA interaction experiments combined with RNA secondary structure mapping revealed that the N-terminal part of CHD4 interacts with an unstructured A-rich region in PAPAS. Deletion or mutation of this sequence abolishes the interaction with CHD4. Stress-dependent up-regulation of PAPAS is accompanied by dephosphorylation of CHD4 at three serine residues, which enhances the interaction of CHD4/NuRD with RNA and reinforces repression of rDNA transcription. The results emphasize the function of lncRNAs in guiding chromatin remodeling complexes to specific genomic loci and uncover a phosphorylation-dependent mechanism of CHD4/NuRD-mediated transcriptional regulation.
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