Transcriptome studies have revealed that protein-coding loci within the human genome are overlapped at their 3′-termini by noncoding RNA (ncRNA) transcripts. Small duplex RNAs designed to be fully complementary to these 3′ ncRNAs can modulate transcription of the upstream gene. Robust regulation by designed RNAs suggests that endogenous small RNAs might also recognize 3′ ncRNAs and regulate gene expression. A genome-wide evaluation revealed that sequences immediately downstream of protein-coding genes are enriched with miRNA target sites. We experimentally tested miRNA mimics complementary to the well-characterized 3′-terminus of the human progesterone receptor (PR) gene and observed inhibition of PR transcription. These results suggest that recognition of ncRNA transcripts that overlap gene termini may be a natural function of endogenous small RNAs.