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Abstract
Argonaute proteins (AGOs) are vital components of the RNA-induced silencing complex in gene silencing. AGOs are indispensable for microRNA (miRNA) biogenesis as well as function, and are intracellularly localized to both the cytoplasm and the nucleus. Cytoplasmic AGO-miRNA complexes are mainly involved in cleavage or translational repression of target mRNAs while the nuclear ones are engaged in transcriptional gene silencing, methylation, chromatin remodeling, and splicing. In insects, AGO1 and AGO2 are involved in RNA interference and miRNA pathways but the components involved in their trafficking between the nucleus and the cytoplasm are not known. In this study, we found that importin β-4 facilitates AGO1 distribution to the nucleus, which is regulated by aae-miR-981 miRNA. The results also revealed association of prohibitin with AGO1 that may play an important role in its stability. Importantly, we found that AGO1 distribution to the nucleus is blocked by Wolbachia, an endosymbiotic bacterium introduced into the Dengue vector, Aedes aegypti. Our results provide basic mechanisms on intracellular trafficking of AGO1 in insects and how this may be altered by Wolbachia, which may affect trafficking of miRNAs to the nucleus leading to alteration in epigenetic effects.
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Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We would like to thank David Morgenstern from the Institute of Molecular Bioscience at UQ for sequencing proteins. This project was supported by the National Health and Medical Research Council (APP1062983) to Asgari S and an Australian Research Council DECRA Fellowship (DE120101512) to Hussain M and a grant from the Foundation of the National Institutes of Health through the Grand Challenges in Global Health Initiative of the Bill and Melinda Gates Foundation to O’Neill SL.