title: RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans.
abstract: Messenger RNA translation is regulated by RNA-binding proteins and small non-coding RNAs called microRNAs. Even though we know the majority of RNA-binding proteins and microRNAs that regulate messenger RNA expression, evidence of interactions between the two remain elusive. The role of the RNA-binding protein GLD-1 as a translational repressor is well studied during Caenorhabditis elegans germline development and maintenance. Possible functions of GLD-1 during somatic development and the mechanism of how GLD-1 acts as a translational repressor are not known. Its human homologue, quaking (QKI), is essential for embryonic development. Here, we report that the RNA-binding protein GLD-1 in C. elegans affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that nhl-2 and vig-1, two known modulators of miRNA function, genetically interact with GLD-1. gld-1 mutations enhance multiple phenotypes conferred by mir-35 and let-7 family mutants during somatic development. We used stable isotope labelling with amino acids in cell culture to globally analyse the changes in the proteome conferred by let-7 and gld-1 during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in let-7 and gld-1 mutants. The link between GLD-1 and miRNA-mediated gene regulation is further supported by its biochemical interaction with ALG-1, CGH-1 and PAB-1, proteins implicated in miRNA regulation. Overall, we have uncovered genetic and biochemical interactions between GLD-1 and miRNA pathways.
authors.affiliation: Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Alper
authors.initials: A
authors.lastname: Akay
authors.forename: Ashley
authors.initials: A
authors.lastname: Craig
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lehrbach
authors.forename: Mark
authors.initials: M
authors.lastname: Larance
authors.forename: Ehsan
authors.initials: E
authors.lastname: Pourkarimi
authors.forename: Jane E
authors.initials: JE
authors.lastname: Wright
authors.forename: Angus
authors.initials: A
authors.lastname: Lamond
authors.forename: Eric
authors.initials: E
authors.lastname: Miska
authors.forename: Anton
authors.initials: A
authors.lastname: Gartner
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D034622:RNA Interference / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D015398:Signal Transduction; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C094448:GLD-1 protein, C elegans; C570417:MIRN35 microRNA, C elegans; D035683:MicroRNAs; C539315:NHL-2 protein, C elegans; D009687:Nuclear Proteins; C490832:QKI protein, human; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C539742:VIG-1 protein, C elegans; C458499:cdl-1 protein, C elegans; C474488:let-7 microRNA, C elegans; D039221:mRNA Cleavage and Polyadenylation Factors
keywords: Caenorhabditis elegans; SILAC; gld-1; let-7; miRNA