Antisense transcripts are targets for activating small RNAs.

Agents that activate expression of specific genes to probe cellular pathways or alleviate disease would go beyond existing approaches for controlling gene expression. Duplex RNAs complementary to promoter regions can repress or activate gene expression. The mechanism of these promoter-directed antigene RNAs (agRNAs) has been obscure. Other work has revealed noncoding transcripts that overlap mRNAs. The function of these noncoding transcripts is also not understood. Here we link these two sets of enigmatic results. We find that antisense transcripts are the target for agRNAs that activate or repress expression of progesterone receptor (PR). agRNAs recruit Argonaute proteins to PR antisense transcripts and shift localization of the heterogeneous nuclear ribonucleoprotein-k, RNA polymerase II and heterochromatin protein 1 gamma. Our data demonstrate that antisense transcripts have a central role in recognition of the PR promoter by both activating and inhibitory agRNAs.