Genes 2013, 4(2), 226-243; https://doi.org/10.3390/genes4020226
High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1
1
Department of Genetics, Geisel School of Medicine, Dartmouth College, Hanover New Hampshire, USA
2
Bio5 Institute, University of Arizona, Tucson Arizona, USA
3
Department of Plant Sciences, University of Arizona, Tucson Arizona, USA
*
Author to whom correspondence should be addressed.
Received: 28 March 2013 / Revised: 9 April 2013 / Accepted: 23 April 2013 / Published: 29 April 2013
(This article belongs to the Special Issue Gene Silencing)
Abstract
Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity to a BRCA1 intron is sufficient for downregulation of BRCA1 mRNA. These observations suggest that transcriptional activation of SINEs could contribute to a novel mechanism of RNA mediated post-transcriptional silencing of human genes. View Full-TextKeywords:
SINE; retrotransposon; BRCA1; post-transcriptional; gene regulation
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Peterson, M.; Chandler, V.L.; Bosco, G. High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1. Genes 2013, 4, 226-243.