The molecular dynamics of long noncoding RNA control of transcription in PTEN and its pseudogene.
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.
['Lister|Nicholas|N|', 'Shevchenko|Galina|G|', 'Walshe|James L|JL|', 'Groen|Jessica|J|', 'Johnsson|Per|P|', 'Vidarsdóttir|Linda|L|', 'Grander|Dan|D|', 'Ataide|Sandro F|SF|', 'Morris|Kevin V|KV|']
D002843:Chromatin D042002:Chromatin Assembly and Disassembly D000090205:DNA Methyltransferase 3A D005091:Exons D057809:HEK293 Cells D006801:Humans D056004:Molecular Dynamics Simulation D009690:Nucleic Acid Conformation D051059:PTEN Phosphohydrolase D011401:Promoter Regions, Genetic D011544:Pseudogenes D062085:RNA, Long Noncoding D050436:Regulatory Elements, Transcriptional D017423:Sequence Analysis, RNA D017385:Sequence Homology
PTEN pseudogene DNMT3a epigenetic PTENpg1