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  Integrator is a genome-wide attenuator of non-productive transcription

Lykke-Andersen, S., Zumer, K., Molska, E. Š., Rouvière, J. O., Wu, G., Demel, C., et al. (2020). Integrator is a genome-wide attenuator of non-productive transcription. Molecular Cell, in Press. doi:10.1016/j.molcel.2020.12.014.

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Lykke-Andersen, S., Author
Zumer, K.1, Author              
Molska, E. Š., Author
Rouvière, J. O., Author
Wu, G., Author
Demel, C.1, Author              
Schwalb, B.1, Author              
Schmid, M., Author
Cramer, P.1, Author              
Jensen, T. H., Author
Affiliations:
1Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1863498              

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 Abstract: 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 small nuclear RNA (snRNA) genes, respectively. Here, we monitor CPA- and INT-dependent termination activities genome-wide, including at thousands of previously unannotated transcription units (TUs), producing unstable RNA. We verify the global activity of CPA occurring at pA sites indiscriminately of their positioning relative to the TU promoter. We also identify a global activity of INT, which is 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, the attenuation of non-productive transcription.

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Language(s): eng - English
 Dates: 2020-12-31
 Publication Status: Published online
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2020.12.014
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Title: Molecular Cell
Source Genre: Journal
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