Mechanism of mammalian transcriptional repression by noncoding RNA

Transcription by RNA polymerase II (Pol II) can be repressed by noncoding RNA, including the human RNA Alu. However, the mechanism by which endogenous RNAs repress transcription remains unclear. Here we present cryogenic-electron microscopy structures of Pol II bound to Alu RNA, which reveal that Alu RNA mimics how DNA and RNA bind to Pol II during transcription elongation. Further, we show how distinct domains of the general transcription factor TFIIF control repressive activity. Together, we reveal how a noncoding RNA can regulate mammalian gene expression. Using cryo-electron microscopy and biochemical analysis, the authors reveal the mechanism of transcriptional inhibition by the noncoding RNA Alu and provide insights into relief of inhibition by the general transcription factor TFIIF.