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J Biol Chem. 2015 Mar 20;290(12):7463-73. doi: 10.1074/jbc.M115.636365. Epub 2015 Jan 26.

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

Author information

1
From the Immunology Programme and Department of Microbiology, Centre for Life Sciences, and the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, the Laboratory of Adjuvant Innovation and.
2
the Laboratory of Adjuvant Innovation and the Laboratory of Vaccine Science, World Premier International Immunology Frontier Research Center (iFREC), Osaka University, Suita, Osaka 565-0871, Japan.
3
From the Immunology Programme and Department of Microbiology, Centre for Life Sciences, and the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456.
4
From the Immunology Programme and Department of Microbiology, Centre for Life Sciences, and.
5
the Laboratory of Bioinformatics, National Institute of Biomedical Innovation (NIBIO), Ibaraki, Osaka 567-0085, Japan, and.
6
From the Immunology Programme and Department of Microbiology, Centre for Life Sciences, and the NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 117456, stephan_gasser@nuhs.edu.sg.
7
the Laboratory of Adjuvant Innovation and the Laboratory of Vaccine Science, World Premier International Immunology Frontier Research Center (iFREC), Osaka University, Suita, Osaka 565-0871, Japan kenishii@biken.osaka-u.ac.jp.

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.

KEYWORDS:

Antibody S9.6; Cancer; DNA Damage; Innate Immunity; MicroRNA (miRNA); RNA Polymerase III; RNA Transport; RNA:DNA Hybrid; RNase H

PMID:
25623070
PMCID:
PMC4367256
DOI:
10.1074/jbc.M115.636365
[Indexed for MEDLINE]
Free PMC Article

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