Affiliation:
1. Centre for Gene Regulation and Expression, University of Dundee, Dundee DD1 5EH, UK
2. Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
3. Friedrich Miescher Institute for Biomedical Research, Basel 4002, Switzerland
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.
Subject
General Biochemistry, Genetics and Molecular Biology,Immunology,General Neuroscience
Cited by
23 articles.
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