Degradation of non-coding RNAs promotes recycling of termination factors at sites of transcription

A large share of the non-coding transcriptome in yeast is controlled by the Nrd1-Nab3-Sen1 (NNS) complex, which promotes transcription termination of non-coding RNA (ncRNA) genes, and by the nuclear exosome, which limits the steady state levels of the transcripts produced. How global ncRNA levels impinge on cellular functions is a longstanding and important question. Here we show that degradation of ncRNAs by the exosome is required for freeing Nrd1 and Nab3 from the released transcript after termination. In exosome mutants, these factors are sequestered by ncRNAs and cannot be efficiently recycled to sites of transcription, which induces termination defects genome-wide. ncRNA-dependent, genome-wide termination defects can be recapitulated by the expression of a degradation-resistant, circular RNA containing a natural NNS target in exosome proficient cells. Our results have important implications for the mechanism of termination, the general impact of ncRNAs on cellular physiology and the importance of nuclear ncRNA degradation.