Dejima Katsufumi, Imae Rieko, Suehiro Yuji, Yoshida Keita, Mitani Shohei
Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
iScience. 2023 May 19;26(6):106930. doi: 10.1016/j.isci.2023.106930. eCollection 2023 Jun 16.
Double-stranded RNA (dsRNA) regulates gene expression in a sequence-dependent manner. In , 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 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 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 mutants showed altered RNAi activity. Based on these results and our analysis using transgenic Zn reporters, we propose that ZIPT-9-dependent Zn homeostasis, rather than overall cytosolic Zn, modulates systemic RNAi activity. Our findings reveal a previously unknown function of zinc transporters in negative RNAi regulation.
双链RNA（dsRNA）以序列依赖的方式调节基因表达。在[具体情境未提及]中，dsRNA在体内扩散并导致系统性RNA沉默。尽管已经通过遗传学方法鉴定了几个参与系统性RNA干扰的基因，但介导系统性RNA干扰的分子在很大程度上仍然未知。在这里，我们鉴定出ZIPT-9，它是ZIP9/SLC39A9的同源物，作为系统性RNA干扰的广谱负调节因子。我们表明，RSD-3、SID-3和SID-5在遗传学上并行作用以实现有效的RNA干扰，并且[具体突变体未明确]突变体抑制了所有突变体的RNA干扰缺陷。对SLC30和SLC39家族基因的全套缺失突变体的分析表明，只有[具体突变体未明确]突变体显示出改变的RNA干扰活性。基于这些结果以及我们使用转基因锌报告基因的分析，我们提出ZIPT-9依赖的锌稳态，而不是整体胞质锌，调节系统性RNA干扰活性。我们的发现揭示了锌转运体在负性RNA干扰调节中以前未知的功能。
