Integrator is a genome-wide attenuator of non-productive transcription [article]

Søren Lykke-Andersen, Kristina Žumer, Ewa Šmidová Molska, Guifen Wu, Jérôme Olivier Rouvière, Carina Demel, Björn Schwalb, Manfred Schmid, Patrick Cramer, Torben Heick Jensen
2020 bioRxiv   pre-print
Termination of RNA polymerase II (RNAPII) transcription in metazoans relies largely on the Cleavage and Polyadenylation (CPA) and Integrator (INT) complexes originally found to act at the ends of protein-coding and snRNA genes, respectively. Here we monitor CPA- and INT-dependent termination activities genome-wide, including over 8000 previously unannotated transcription units (TUs), that produce unstable RNA. We verify the global activity of CPA, that occurs at pA sites indiscriminately of
more » ... r positioning relative to the TU promoter. We also identify a global activity of INT, which is, however, largely sequence-independent and restricted to a ~3 kb promoter-proximal region. Our analyses suggest two functions of genome-wide INT activity; it dampens transcriptional output from weak promoters and it provides quality-control of RNAPII complexes, that are unfavorably configured for transcriptional elongation. We suggest that the function of INT in stable snRNA production is an exception from its general cellular role, attenuation of non-productive transcription.
doi:10.1101/2020.07.17.208702 fatcat:odiporjos5bzddlkfsbasgnapu