Regulation of gene expression is essential for normal physiology and development. One of the ways cells regulate gene expression is through a class of non-coding RNAs called microRNAs (miRNAs). miRNAs associate with Argonaute proteins to form miRNA Induced Silencing Complexes (miRISCs), which post-transcriptionally repress gene expression by targeting mRNA 3'UTRs through partial sequence complementarity. We previously identified HRPA-1 (Heterogenous nuclear RibonucleoProtein (HnRNP) A homolog) as a potential interactor of miRISC. Using an endogenous GFP tag, we show that HRPA-1 is ubiquitously expressed throughout C. elegans development with a strong expression in the nucleus. To determine whether HRPA-1 is functionally important for miRNAs, we knocked down
hrpa-1 in sensitized miRNA mutant backgrounds.
mir-48 mir-241(nDf51) animals show a partially penetrant heterochronic phenotype including delayed expression of the adult collagen
col-19::gfp. Deletion of
hrpa-1 in
mir-48 mir-241(nDf51) background enhanced these defects suggesting that
hrpa-1 is important for
let-7 family miRNA activity. Similarly, loss of
hrpa-1 strongly enhanced developmental defects associated with other miRNA sensitized mutants,
lsy-6(
ot150) and
let-7(
n2853). Small RNA sequencing revealed depletion of
hrpa-1 results in an increase of mature miRNA levels for some miRNAs and a decrease in mature miRNA levels for other miRNAs. Surprisingly,
let-7 miRNA levels increased upon
hrpa-1 depletion, while miR-84 and
lsy-6 miRNA levels remained unchanged. Overall, our data suggest that HRPA-1 activity is important for regulation of gene expression and directly or indirectly interacts with miRNAs, potentially by affecting miRNA biogenesis. To identify the effects of loss of
hrpa-1 on global gene expression, we performed RNAseq and identified 143 genes that were significantly disrupted. Interestingly, a predicted interactor of HRPA-1, R06C1.4 and a homolog of a yeast component of cleavage and polyadenylation factor I (CF I), was found to be significantly downregulated. RNAi knockdown of R06C1.4 partially recapitulated the enhancement effects on miRNA sensitized mutant developmental phenotypes observed with
hrpa-1 loss. We propose that
hrpa-1 could be affecting miRNAs by (i) influencing biogenesis or processing, and (ii) potentially affecting miRNA targets through mRNA processing mechanisms.