title: miR-58 family and TGF-β pathways regulate each other in Caenorhabditis elegans.
abstract: Despite the fact that microRNAs (miRNAs) modulate the expression of around 60% of protein-coding genes, it is often hard to elucidate their precise role and target genes. Studying miRNA families as opposed to single miRNAs alone increases our chances of observing not only mutant phenotypes but also changes in the expression of target genes. Here we ask whether the TGF-β signalling pathways, which control many animal processes, might be modulated by miRNAs in Caenorhabditis elegans. Using a mutant for four members of the mir-58 family, we show that both TGF-β Sma/Mab (controlling body size) and TGF-β Dauer (regulating dauer, a stress-resistant larval stage) are upregulated. Thus, mir-58 family directly inhibits the expression of dbl-1 (ligand), daf-1, daf-4 and sma-6 (receptors) of TGF-β pathways. Epistasis experiments reveal that whereas the small body phenotype of the mir-58 family mutant must invoke unknown targets independent from TGF-β Sma/Mab, its dauer defectiveness can be rescued by DAF-1 depletion. Additionally, we found a negative feedback loop between TGF-β Sma/Mab and mir-58 and the related mir-80. Our results suggest that the interaction between mir-58 family and TGF-β genes is key on decisions about animal growth and stress resistance in C. elegans and perhaps other organisms.
authors.affiliation: Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain.
authors.forename: María Pilar
authors.initials: MP
authors.lastname: de Lucas
authors.affiliation: Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain.
authors.forename: Alberto G
authors.initials: AG
authors.lastname: Sáez
authors.affiliation: Unidad Funcional de Investigación de Enfermedades Crónicas, Instituto de Salud Carlos III, 28220, Majadahonda, Madrid, Spain encarnilozano@gmail.com.
authors.forename: Encarnación
authors.initials: E
authors.lastname: Lozano
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D049628:Body Size; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007814:Larva / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta