Beschreibung:
<jats:p>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<jats:italic>Caenorhabditis elegans</jats:italic>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<jats:italic>C. elegans</jats:italic>affects multiple microRNA pathways and interacts with proteins required for microRNA function. Using genome-wide RNAi screening, we found that<jats:italic>nhl-2</jats:italic>and<jats:italic>vig-1</jats:italic>, two known modulators of miRNA function, genetically interact with GLD-1.<jats:italic>gld-1</jats:italic>mutations enhance multiple phenotypes conferred by<jats:italic>mir-35</jats:italic>and<jats:italic>let-7</jats:italic>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<jats:italic>let-7</jats:italic>and<jats:italic>gld-1</jats:italic>during animal development. We identified the histone mRNA-binding protein CDL-1 to be, in part, responsible for the phenotypes observed in<jats:italic>let-7</jats:italic>and<jats:italic>gld-1</jats:italic>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.</jats:p>