Molecular Mechanism Of Long Non-Coding RNA In Regulating Toxicity Of Nanopolystyrene And Multi-Walled Carbon Nanotubes In Caenorhabditis Elegans

In recent years,long non-coding RNAs(lncRNAs)have become a research hotspot rather than transcriptional noise.A large amount of studies have shown that lncRNAs are involved in the control of a variety of important biological processes in plants or animals.Caenorhabditis elegans is very sensitive to environmental toxicants,which makes it an important animal model for toxicology research.Using this animal model,the underling mechanisms of lncRNAs involved in the control of aging and cell proliferation have been examined.However,the molecular mechanisms of lncRNAs involved in the control of toxicity of engineered nanomaterials remain largely unclear.In this study,we focus on the elucidation of molecular mechanisms of lncRNAs in regulating toxicity of nanomaterials(such as nanopolystyrene(PS-NPs)and multi-walled carbon nanotubes(MWCNTs))in nematodes.1、Molecular mechanism of intestine lncRNA in regulating the toxicity of nanopolystyreneIntestinal barrier plays a crucial function during the control of toxicity of PS-NPs in nematodes.Most of the PS-NPs were translocated and accumulated in the intestine after exposure.However,the molecular mechanism of intestine lncRNAs in regulating the toxicity of PS-NPs remain unclear.We here used C.elegans as an animal model to determine intestinal lncRNAs dysregulated by PS-NPs.We found four intestine lncRNAs(linc-61,linc-50,linc-9 and linc-2)in response to PS-NPs and with the function in controlling PS-NPs toxicity.The alteration in expressions of these four intestinal lncRNAs reflected a protective response to PS-NPs exposure.During the response to PS-NPs,limited number of transcriptional factors functioned as the downstream targets of these four lncRNAs.linc-2 acted upstream of DAF-16,linc-9acted upstream of NHR-77,linc-50 functioned upstream of DAF-16,and linc-61 regulated the functions of DAF-16,DVE-1 and FKH-2 to control PS-NPs toxicity.The obtained data demonstrated the important role of lncRNAs in intestinal barrier to mediate a protective response to PS-NPs exposure at low concentrations.2、Molecular mechanism of germline linc-7 in regulating to the transgenerational toxicity of MWCNTsAfter the exposure,the MWCNTs could be largely translocated and accumulated in the gonad of nematodes.However,the molecular mechanism of germline lncRNAs in regulating the transgenerational MWCNTs toxicity remains unknown.Using C.elegans as an animal model,we identified germline lncRNAs dysregulated by MWCNTs exposure.The germline lncRNA of linc-7 was shown to be involved in the control of transgenerational MWCNTs toxicity.In the germline,linc-7 regulated the transgenerational MWCNTs toxicity by targeting transcriptional factor DAF-12 and affecting function of TBH-1-mediated octopamine signal.During the control of transgenerational MWCNTs toxicity,octopamine could transgenerationally affect the function of corresponding receptors of SER-6 and OCTR-1 in the intestine.In the intestine,SER-6 and OCTR-1 further regulated the transgenerational MWCNTs toxicity by activating or inhibiting activity of transcriptional factor ELT-2.Our data demonstrated the important function of germline lncRNAs in regulating transgenerational MWCNTs toxicity.On the one hand,we found that the intestinal lncRNAs(such as linc-2,linc-9,linc-50 and linc-61)could regulate the PS-NPs toxicity by targeting to limited number of downstream transcriptional factors.On the other hand,the germline lncRNAs(such as linc-7)could regulate the transgenerational MWCNTs toxicity by modulating the transgenerational signal communication of octopamine mediated by DAF-12.The obtained data will be helpful for our understanding the function of lncRNAs in regulating the toxicity of nanomaterials.