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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Eaton JD,Francis L,Davidson L,West Sdoi
10.1101/gad.332833.119subject
Has Abstractpub_date
2020-01-01 00:00:00pages
132-145issue
1-2eissn
0890-9369issn
1549-5477pii
gad.332833.119journal_volume
34pub_type
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