title: Methylmercury exposure increases lipocalin related (lpr) and decreases activated in blocked unfolded protein response (abu) genes and specific miRNAs in Caenorhabditis elegans.
abstract: Methylmercury (MeHg) is a persistent environmental and dietary contaminant that causes serious adverse developmental and physiologic effects at multiple cellular levels. In order to understand more fully the consequences of MeHg exposure at the molecular level, we profiled gene and miRNA transcripts from the model organism Caenorhabditis elegans. Animals were exposed to MeHg (10 μM) from embryo to larval 4 (L4) stage and RNAs were isolated. RNA-seq analysis on the Illumina platform revealed 541 genes up- and 261 genes down-regulated at a cutoff of 2-fold change and false discovery rate-corrected significance q < 0.05. Among the up-regulated genes were those previously shown to increase under oxidative stress conditions including hsp-16.11 (2.5-fold), gst-35 (10.1-fold), and fmo-2 (58.5-fold). In addition, we observed up-regulation of 6 out of 7 lipocalin related (lpr) family genes and down regulation of 7 out of 15 activated in blocked unfolded protein response (abu) genes. Gene Ontology enrichment analysis highlighted the effect of genes related to development and organism growth. miRNA-seq analysis revealed 6-8 fold down regulation of mir-37-3p, mir-41-5p, mir-70-3p, and mir-75-3p. Our results demonstrate the effects of MeHg on specific transcripts encoding proteins in oxidative stress responses and in ER stress pathways. Pending confirmation of these transcript changes at protein levels, their association and dissociation characteristics with interaction partners, and integration of these signals, these findings indicate broad and dynamic mechanisms by which MeHg exerts its harmful effects.
authors.affiliation: A. I. Virtanen Institute for Molecular Sciences, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland. Electronic address: martina.rudgalvyte@uef.fi.
authors.forename: Martina
authors.initials: M
authors.lastname: Rudgalvyte
authors.forename: Natalia
authors.initials: N
authors.lastname: VanDuyn
authors.forename: Vuokko
authors.initials: V
authors.lastname: Aarnio
authors.forename: Liisa
authors.initials: L
authors.lastname: Heikkinen
authors.forename: Juhani
authors.initials: J
authors.lastname: Peltonen
authors.forename: Merja
authors.initials: M
authors.lastname: Lakso
authors.forename: Richard
authors.initials: R
authors.lastname: Nass
authors.forename: Garry
authors.initials: G
authors.lastname: Wong
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007814:Larva / Q000187:drug effects / Q000378:metabolism; D054834:Lipocalins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008767:Methylmercury Compounds / Q000633:toxicity*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family / Q000187:drug effects; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D034622:RNA Interference; D018510:RNA, Helminth / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D056811:Unfolded Protein Response / Q000187:drug effects*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004785:Environmental Pollutants; D054834:Lipocalins; D008767:Methylmercury Compounds; D035683:MicroRNAs; D018510:RNA, Helminth; C004925:methylmercuric chloride
keywords: Blocked unfolded protein response; ER stress; Heavy metal; Next-generation sequencing; Oxidative stress