A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes.
dc.contributor.author | Eaton, JD | |
dc.contributor.author | Francis, L | |
dc.contributor.author | Davidson, L | |
dc.contributor.author | West, S | |
dc.date.accessioned | 2020-01-10T11:25:58Z | |
dc.date.issued | 2019-12-05 | |
dc.description.abstract | The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is important. Here, we describe a single mechanism incorporating features of both models. We show that termination is completely abolished by rapid elimination of CPSF73, which causes very extensive transcriptional readthrough genome-wide. This is because CPSF73 functions upstream of modifications to the elongation complex and provides an entry site for the XRN2 torpedo. Rapid depletion of XRN2 enriches these events that we show are underpinned by protein phosphatase 1 (PP1) activity, the inhibition of which extends readthrough in the absence of XRN2. Our results suggest a combined allosteric/torpedo mechanism, in which PP1-dependent slowing down of polymerases over termination regions facilitates their pursuit/capture by XRN2 following PAS processing. | en_GB |
dc.description.sponsorship | Lister Institute of Preventative Medicine | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.identifier.citation | Vol. 34, pp. 132 - 145 | en_GB |
dc.identifier.doi | 10.1101/gad.332833.119 | |
dc.identifier.grantnumber | WT107791/Z/15/Z | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/40345 | |
dc.language.iso | en | en_GB |
dc.publisher | Cold Spring Harbor Laboratory Press | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/31805520 | en_GB |
dc.rights | © 2020 Eaton et al.; Published by Cold Spring Harbor Laboratory Press This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.subject | CPSF73 | en_GB |
dc.subject | PP1 | en_GB |
dc.subject | RNA polymerase II | en_GB |
dc.subject | XRN2 | en_GB |
dc.subject | antisense oligo | en_GB |
dc.subject | polyadenylation signal | en_GB |
dc.subject | transcriptional termination | en_GB |
dc.title | A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes. | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2020-01-10T11:25:58Z | |
dc.identifier.issn | 0890-9369 | |
exeter.place-of-publication | United States | en_GB |
dc.description | This is the final version. Available on open access from Cold Spring Harbor Laboratory Press via the DOI in this record. | en_GB |
dc.identifier.eissn | 1549-5477 | |
dc.identifier.journal | Genes and Development | en_GB |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-11-18 | |
exeter.funder | ::Lister Institute of Preventative Medicine | en_GB |
exeter.funder | ::Wellcome Trust | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2020-01-01 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2020-01-10T11:17:20Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2020-01-22T11:12:06Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © 2020 Eaton et al.; Published by Cold Spring Harbor Laboratory Press
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.