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Accession: PRJNA554298 ID: 554298

Control of RNA pol II speed by PNUTS-PP1 and Spt5 dephosphorylation facilitates termination by a “sitting duck torpedo” mechanism (human)

See Genome Information for Homo sapiens
Control of transcription speed, which influences many co-transcriptional processes, is poorly understood. We report that PNUTS-PP1 phosphatase is a negative regulator of RNA pol II elongation rate. The PNUTS W401A mutation, which disrupts PP1 binding, causes genome-wide acceleration of transcription associated with hyper-phosphorylation of the Spt5 elongation factor. Immediately downstream of poly(A) sites, pol II decelerates from >2kb/min to <1 kb/min, which correlates with Spt5 dephosphorylation. Pol II deceleration and Spt5 dephosphorylation require poly(A) site recognition and the PNUTS-PP1 complex, which is in turn necessary for transcription termination. These results lead to a new model for termination, the “sitting duck torpedo” mechanism, where poly(A) site-dependent deceleration caused by PNUTS-PP1 and Spt5 dephosphorylation is required to convert pol II into a viable target for the Xrn2 terminator exonuclease. Spt5 and its bacterial homologue NusG therefore have related functions controlling kinetic competition between RNA polymerases and the termination factors that pursue them. Overall design: Transcription elongation rates were determined within gene bodies and dwonstream of termination sites by mapping pol II positions after release of a DRB block or after inhibiting initiation with triptolide. Elongation rates were estimated under conditions where termination was inhibited by a dominant negative mutants of the exonuclease Xrn2 or the PP! nuclear targeting subunit, PNUTS. In addition Spt5 phosphorylation was measured by ChIP and found to correlate closely with chages in elongation rate.
AccessionPRJNA554298; GEO: GSE134198
ScopeMultiisolate
OrganismHomo sapiens[Taxonomy ID: 9606]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo; Homo sapiens
PublicationsCortazar MA et al., "Control of RNA Pol II Speed by PNUTS-PP1 and Spt5 Dephosphorylation Facilitates Termination by a "Sitting Duck Torpedo" Mechanism.", Mol Cell, 2019 Dec 19;76(6):896-908.e4
Grants
  • "Coupling of transcription with nascent pre-mRNA metabolism" (Grant ID R35 GM118051, National Institute of General Medical Sciences)
SubmissionRegistration date: 12-Jul-2019
Bentley, BMG, UCD AMC
RelevanceMedical
Project Data:
Resource NameNumber
of Links
Sequence data
SRA Experiments84
Publications
PubMed1
PMC1
Other datasets
BioSample84
GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Supplementary Mbytes15544
SRA Data Details
ParameterValue
Data volume, Gbases391
Data volume, Tbytes0.14

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