RNA-binding protein GLD-1/quaking genetically interacts with the mir-35 and the let-7 miRNA pathways in Caenorhabditis elegans.
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.
Mesh Terms:
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Gene Expression Regulation, Developmental, Humans, MicroRNAs, Mutation, Nuclear Proteins, Phenotype, RNA Interference, RNA-Binding Proteins, Ribonucleoproteins, Signal Transduction, mRNA Cleavage and Polyadenylation Factors
Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Carrier Proteins, Gene Expression Regulation, Developmental, Humans, MicroRNAs, Mutation, Nuclear Proteins, Phenotype, RNA Interference, RNA-Binding Proteins, Ribonucleoproteins, Signal Transduction, mRNA Cleavage and Polyadenylation Factors
Open Biol
Date: Nov. 20, 2013
PubMed ID: 24258276
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