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Abstract
Small noncoding RNAs function in concert with Argonaute (Ago) proteins to regulate
gene expression at the level of transcription, mRNA stability, or translation. Ago
proteins bind small RNAs and form the core of silencing complexes. Here, we report
the analysis of small RNAs associated with human Ago1 and Ago2 revealed by immunoprecipitation
and deep sequencing. Among the reads, we find small RNAs originating from the small
nucleolar RNA (snoRNA) ACA45. Moreover, processing of ACA45 requires Dicer activity
but is independent of Drosha/DGCR8. Using bioinformatic prediction algorithms and
luciferase reporter assays, we uncover the mediator subunit CDC2L6 as one potential
mRNA target of ACA45 small RNAs, suggesting a role for ACA45-processing products in
posttranscriptional gene silencing. We further identify a number of human snoRNAs
with microRNA (miRNA)-like processing signatures. We have, therefore, identified a
class of small RNAs in human cells that originate from snoRNAs and can function like
miRNAs.