hnRNPA1/2 homolog hrpa-1 coordinates with miRNAs to regulate gene expression during C. elegans development.

Abstract

microRNAs (miRNAs) are small non-coding RNAs that play crucial roles in development and in disease. miRNAs associate with Argonaute proteins to form miRNA Induced Silencing Complexes (miRISCs), which post-transcriptionally repress gene expression. miRNA-mediated gene repression itself is subject to regulation by factors that can affect miRNA biogenesis or function. We previously identified HRPA-1, an hnRNPA/B homolog, as a putative physical interactor of miRNAs. Here, we report characterizations of both physical and genetic interactions between HRPA-1 and miRISC components. We confirmed HRPA-1 precipitation in let-7 and miR-58 pulldowns and detected an interaction between HRPA-1 and Argonaute. Deletion of hrpa-1 in a mir-48 mir-241(nDf51) background enhanced the mir-48 mir-241 developmental defects, suggesting that hrpa-1 may be important for let-7 family miRNA activity. Similarly, loss of hrpa-1 strongly enhanced developmental defects associated with two other miRNA mutants, lsy-6(ot150) and let-7(n2853). Depletion of HRPA-1 modestly disrupted miRNA levels and affected global gene expression profiles. We identified a potential target of hrpa-1, R06C1.4, whose knockdown partially recapitulates the hrpa-1(-) effects on miRNA mutant phenotypes. Overall, we demonstrate hrpa-1 and R06C1.4 roles in C. elegans developmental timing regulation and propose models describing possible coordinating modes of gene regulation by HRPA-1 and miRNAs.