Abstract
Multi-walled carbon nanotubes (MWCNTs) have been produced and applied for diverse purposes. MWCNTs can potentially cause the adverse effects on organisms. MicroRNA let-7 and its targets of HBL-1 and LIN-41 play a central role in regulating developmental timing by acting as a developmental switch. The sequence of let-7 and the underlying mechanisms for let-7 in the control of developmental timing are conserved among different species. In this study, we investigated the potential effect of MWCNTs exposure on the molecular basis for developmental timing mediated by let-7 and its targets of HBL-1 and LIN-41. MWCNTs exposure decreased let-7 expression, and increased expressions of hbl-1 and lin-41. let-7 mutant was resistant to MWCNTs toxicity, whereas hbl-1 or lin-41 mutant was susceptible to MWCNTs toxicity. hbl-1 or lin-41 mutant suppressed the resistance of let-7 mutant to MWCNTs toxicity. HBL-1 acted upstream of TIR-1, an adaptor protein, and SYM-1, a protein containing leucine-rich repeats, and ALG-1 and ALG-2, two RDE-1 proteins related to RNA interference (RNAi) pathway, acted upstream of LIN-41 to regulate MWCNTs toxicity. Moreover, we identified a feedback loop between let-7 and its targets of HBL-1 and LIN-41 in the regulation of MWCNTs toxicity. The observed increase in let-7::GFP expression in MWCNTs exposed nematodes with mutation of hbl-1 or lin-41 implied that a feedback mechanism may exist to strengthen the function of let-7 suppression in protecting the animals from MWCNTs toxicity. Our results demonstrate the protection function of let-7 suppression for animals from MWCNTs toxicity by conferring a robust developmental timing control. Our results highlight the importance of molecular basis for developmental timing in influencing MWCNTs toxicity.
Highlights
Multi-walled carbon nanotubes (MWCNTs) have been produced and applied for diverse purposes
We investigated the potential effect of MWCNTs exposure on the molecular basis for developmental timing mediated by let-7 and its targets of HBL-1 and LIN-41 using in vivo assay system of C. elegans
Effect of MWCNTs exposure on let-7 expression Our previous studies have demonstrated that prolonged exposure to MWCNTs at concentrations more than 1 μg/L could result in the significant induction of intestinal reactive oxygen species (ROS) production and decrease in locomotion behavior in nematodes [18, 21]
Summary
Multi-walled carbon nanotubes (MWCNTs) have been produced and applied for diverse purposes. We investigated the potential effect of MWCNTs exposure on the molecular basis for developmental timing mediated by let-7 and its targets of HBL-1 and LIN-41. MiRNAs have been shown to play important functions in regulating the toxicity of certain carbon-based ENMs, such as MWCNTs and graphene oxide (GO) [25,26,27,28,29]. It has been shown that let-7 regulates the timing of larval and adult transition by acting as a developmental switch, and the sequence and functions of let-7 are conserved among different species [30, 31]. We investigated the potential effect of MWCNTs exposure on the molecular basis for developmental timing mediated by let-7 and its targets of HBL-1 and LIN-41 using in vivo assay system of C. elegans. Our results demonstrated that the miRNA let-7 could be decreased by MWCNTs exposure, and was required for the regulation of MWCNTs toxicity. let-7 further regulated
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