An endomembrane zinc transporter negatively regulates systemic RNAi in Caenorhabditis elegans

Katsufumi Dejima; Rieko Imae; Yuji Suehiro; Keita Yoshida; Shohei Mitani

doi:10.1016/j.isci.2023.106930

An endomembrane zinc transporter negatively regulates systemic RNAi in Caenorhabditis elegans

iScience. 2023 May 19;26(6):106930. doi: 10.1016/j.isci.2023.106930. eCollection 2023 Jun 16.

Authors

Katsufumi Dejima¹, Rieko Imae¹, Yuji Suehiro¹, Keita Yoshida¹, Shohei Mitani¹

Affiliation

¹ Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

Abstract

Double-stranded RNA (dsRNA) regulates gene expression in a sequence-dependent manner. In Caenorhabditis elegans, dsRNA spreads through the body and leads to systemic RNA silencing. Although several genes involved in systemic RNAi have been genetically identified, molecules that mediate systemic RNAi remain largely unknown. Here, we identified ZIPT-9, a C. elegans homolog of ZIP9/SLC39A9, as a broad-spectrum negative regulator of systemic RNAi. We showed that RSD-3, SID-3, and SID-5 genetically act in parallel for efficient RNAi, and that zipt-9 mutants suppress the RNAi defects of all the mutants. Analysis of a complete set of deletion mutants for SLC30 and SLC39 family genes revealed that only zipt-9 mutants showed altered RNAi activity. Based on these results and our analysis using transgenic Zn²⁺ reporters, we propose that ZIPT-9-dependent Zn²⁺ homeostasis, rather than overall cytosolic Zn²⁺, modulates systemic RNAi activity. Our findings reveal a previously unknown function of zinc transporters in negative RNAi regulation.

Keywords: Cell biology; Molecular biology.