RNA polymerase III regulates cytosolic RNA:DNA hybrids and intracellular microRNA expression.

Abstract

RNA:DNA hybrids form in the nuclei and mitochondria of cells as transcription-induced R-loops or G-quadruplexes, but exist only in the cytosol of virus-infected cells. Little is known about the existence of RNA:DNA hybrids in the cytosol of virus-free cells, in particular cancer or transformed cells. Here, we show that cytosolic RNA:DNA hybrids are present in various human cell lines, including transformed cells. Inhibition of RNA polymerase III (Pol III), but not DNA polymerase, abrogated cytosolic RNA:DNA hybrids. Cytosolic RNA:DNA hybrids bind to several components of the microRNA (miRNA) machinery-related proteins, including AGO2 and DDX17. Furthermore, we identified miRNAs that are specifically regulated by Pol III, providing a potential link between RNA:DNA hybrids and the miRNA machinery. One of the target genes, exportin-1, is shown to regulate cytosolic RNA:DNA hybrids. Taken together, we reveal previously unknown mechanism by which Pol III regulates the presence of cytosolic RNA:DNA hybrids and miRNA biogenesis in various human cells.

• Authors: Christine Xing'er Koo, Kouji Kobiyama, Yu J Shen, Nina LeBert, Shandar Ahmad, Muznah Khatoo, Taiki Aoshi, Stephan Gasser, Ken J Ishii
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 12 Pg. 7463-73 (Mar 20 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 25623070 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• MicroRNAs
• RNA, Small Interfering
• RNA
• DNA
• RNA Polymerase III

Topics

• Base Sequence
• Cell Line, Tumor
• Cytosol (metabolism)
• DNA (genetics)
• DNA Damage
• Humans
• Mass Spectrometry
• MicroRNAs (genetics)
• Nucleic Acid Hybridization
• Oligonucleotide Array Sequence Analysis
• RNA (genetics)
• RNA Polymerase III (metabolism)
• RNA, Small Interfering