Transcriptional regulation by small RNAs at sequences downstream from 3-2 gene termini

Transcriptome studies reveal many noncoding transcripts overlapping 3-2 gene termini. The function of these transcripts is unknown. Here we have characterized transcription at the progesterone receptor (PR) locus and identified noncoding transcripts that overlap the 3-2 end of the gene. Small RNAs complementary to sequences beyond the 3-2 terminus of PR mRNA modulated expression of PR, recruited argonaute 2 to a 3-2 noncoding transcript, altered occupancy of RNA polymerase II, induced chromatin changes at the PR promoter and affected responses to physiological stimuli. We found that the promoter and 3-2 terminal regions of the PR locus are in close proximity, providing a potential mechanism for RNA-mediated control of transcription over long genomic distances. These results extend the potential for small RNAs to regulate transcription to target sequences beyond the 3-2 termini of mRNA.