The Nrd1-Nab3-Sen1 (NNS) complex is essential for controlling pervasive transcription and generating sn/snoRNAs in S. cerevisiae. The NNS complex terminates transcription of noncoding RNA genes and promotes exosome-dependent processing/degradation of the released transcripts. The Trf4-Air2-Mtr4 (TRAMP) complex polyadenylates NNS target RNAs and favors their degradation. NNS-dependent termination and degradation are coupled, but the mechanism underlying this coupling remains enigmatic. Here we provide structural and functional evidence demonstrating that the same domain of Nrd1p interacts with RNA polymerase II and Trf4p in a mutually exclusive manner, thus defining two alternative forms of the NNS complex, one involved in termination and the other in degradation. We show that the Nrd1-Trf4 interaction is required for optimal exosome activity in vivo and for the stimulation of polyadenylation of NNS targets by TRAMP in vitro. We propose that transcription termination and RNA degradation are coordinated by switching between two alternative partners of the NNS complex.

CEITEC Central European Institute of Technology Masaryk University Brno 62500 Czech Republic; National Centre for Biomolecular Research Faculty of Science Masaryk University Brno 62500 Czech Republic

Centre de Génétique Moléculaire CNRS UPR3404 91190 Gif sur Yvette France

Gene Center Munich and Department of Biochemistry Center for Integrated Protein Science CIPSM Ludwig Maximilians Universität München 81377 Munich Germany

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Yeast Spt6 Reads Multiple Phosphorylation Patterns of RNA Polymerase II C-Terminal Domain In Vitro

Termination of non-coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD-mimicking region in Sen1

RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3'-end extended forms of snRNAs

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PDB
2MOW