Like a conscientious librarian, miRNA can’t seem to resist saying “Shhhh!” whenever the opportunity arises, whether in post-transcriptional or, as a new study suggests, in transcriptional silencing of genes. Although miRNAs were initially thought to suppress gene expression primarily through translational inhibition, recent evidence suggests additional roles for miRNAs in regulating gene expression in the nucleus. To explore whether miRNAs can silence gene expression at the transcriptional level, John Rossi and colleagues at the Beckman Research Institute of the City of Hope and the Norwegian University of Science and Technology searched for potential miRNA target sites in the promoter regions of well-annotated human genes.
The investigators identified 10 miRNAs that were encoded within the promoter regions of known genes and could potentially target their opposite strand sequences in cis to influence gene transcription. One of these miRNAs, miR-320, was encoded in the antisense orientation directly upstream of the POLR3D gene, whose protein product is a subunit of RNA polymerase III. miR-320 was shown to silence POLR3D transcription in mammalian cells through enrichment of the siRNA-binding protein Argonaute-1, the histone methyltransferase EZH2, and tri-methyl histone H3 lysine 27 at the POLR3D promoter. Rossi and co-workers hypothesized that miR-320 directs Agonaute-1 to the miRNA’s complementary target site within the POLR3D promoter, which results in the recruitment of other proteins that silence transcription by an epigenetic mechanism. Get all the details in PNAS, October 2008.