期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 37, 页码 9942-9947出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1621490114
关键词
PTEN; DNMT3a; pseudogene; PTENpg1; epigenetic
资金
- National Institute of Allergy and Infectious Diseases [P01 AI099783-01]
- NIH [DK104681-02]
- ARC [FT130100572]
- Swedish Research Council [K2013-64X-20432-07-4]
- Swedish Cancer Foundation [15 0768]
- Radiumhemmets Research Funds [144063]
- Swedish Childhood Cancer Foundation [PR2015-0009]
- Australian Research Council [FT130100572] Funding Source: Australian Research Council
RNA has been found to interact with chromatin and modulate gene transcription. In human cells, little is known about how long noncoding RNAs (lncRNAs) interact with target loci in the context of chromatin. We find here, using the phosphatase and tensin homolog (PTEN) pseudogene as a model system, that antisense lncRNAs interact first with a 5' UTR-containing promoter-spanning transcript, which is then followed by the recruitment of DNA methyltransferase 3a (DNMT3a), ultimately resulting in the transcriptional and epigenetic control of gene expression. Moreover, we find that the lncRNA and promoter-spanning transcript interaction are based on a combination of structural and sequence components of the antisense lncRNA. These observations suggest, on the basis of this one example, that evolutionary pressures may be placed on RNA structure more so than sequence conservation. Collectively, the observations presented here suggest a much more complex and vibrant RNA regulatory world may be operative in the regulation of gene expression.
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