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A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes

ABSTRACT: The so-called allosteric and torpedo models have been used for the past thirty years to explain how transcription terminates on protein-coding genes. The former invokes conformational changes in the transcription complex and the latter involves degradation of the downstream product of poly(A) signal (PAS) processing. Here, we describe a single mechanism incorporating features of both models. We show that CPSF73 is indispensable for transcriptional termination on protein-coding and its loss causes profound read-through genome-wide. CPSF73 functions upstream of allosteric modifications to the elongation complex that cause Pol II to slow down after the PAS. This state is enriched by rapid depletion of XRN2 and promoted by protein phosphatase 1 (PP1), the inhibition of which confers runaway read-through in the absence of XRN2. These allosteric changes facilitate XRN2-dependent termination, by aiding its capture of Pol II, rather than constituting a termination pathway in themselves. Our experiments unify the long-standing allosteric and torpedo models for transcriptional termination.

ORGANISM(S): Homo sapiens

PROVIDER: GSE137727 | GEO | 2020/01/21

REPOSITORIES: GEO

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Xrn2 accelerates termination by RNA polymerase II, which is underpinned by CPSF73 activity

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2018-02-13 | GSE109003 | GEO

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mRNA decapping factors and the exonuclease Xrn2 function in widespread premature termination of RNA polymerase II transcription

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