As regulators of gene expression in multicellular organisms, microRNAs (miRNAs) are crucial for growth and development. Although a plethora of factors involved in their biogenesis and action in Arabidopsis () has been described, these processes and their fine-tuning are not fully understood. Here, we used plants expressing an artificial miRNA target mimic (MIM) to screen for negative regulators of miR156. We identified a new mutant allele of the F-box gene (; At3G61590), -, as a suppressor of the -induced developmental and molecular phenotypes. In plants, levels of some endogenous miRNAs are increased and their mRNA targets decreased. Plants constitutively expressing full-length HWS-but not a truncated version lacking the F-box domain-display morphological and molecular phenotypes resembling those of mutants defective in miRNA biogenesis and activity. In combination with such mutants, loses its delayed floral organ abscission ("skirt") phenotype, suggesting epistasis. Also, the transcriptome profile partially resembles those of well-known miRNA mutants -, -, and -, pointing to a role in a common pathway. We thus propose HWS as a novel, F-box dependent factor involved in miRNA function.