Distinct Cdk9-phosphatase switches act at the beginning and end of elongation by RNA polymerase II.
Cyclin-Dependent Kinase 9
/ antagonists & inhibitors
HCT116 Cells
Humans
Nuclear Proteins
/ genetics
Phosphorylation
Positive Transcriptional Elongation Factor B
/ metabolism
RNA Interference
RNA Polymerase II
/ genetics
Receptors, Neuropeptide Y
/ metabolism
Transcription, Genetic
/ physiology
Transcriptional Elongation Factors
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 08 2020
28 08 2020
Historique:
received:
11
06
2020
accepted:
10
08
2020
entrez:
30
8
2020
pubmed:
30
8
2020
medline:
18
9
2020
Statut:
epublish
Résumé
Reversible phosphorylation of Pol II and accessory factors helps order the transcription cycle. Here, we define two kinase-phosphatase switches that operate at different points in human transcription. Cdk9/cyclin T1 (P-TEFb) catalyzes inhibitory phosphorylation of PP1 and PP4 complexes that localize to 3' and 5' ends of genes, respectively, and have overlapping but distinct specificities for Cdk9-dependent phosphorylations of Spt5, a factor instrumental in promoter-proximal pausing and elongation-rate control. PP1 dephosphorylates an Spt5 carboxy-terminal repeat (CTR), but not Spt5-Ser666, a site between Kyrpides-Ouzounis-Woese (KOW) motifs 4 and 5, whereas PP4 can target both sites. In vivo, Spt5-CTR phosphorylation decreases as transcription complexes pass the cleavage and polyadenylation signal (CPS) and increases upon PP1 depletion, consistent with a PP1 function in termination first uncovered in yeast. Depletion of PP4-complex subunits increases phosphorylation of both Ser666 and the CTR, and promotes redistribution of promoter-proximally paused Pol II into gene bodies. These results suggest that switches comprising Cdk9 and either PP4 or PP1 govern pause release and the elongation-termination transition, respectively.
Identifiants
pubmed: 32859893
doi: 10.1038/s41467-020-18173-6
pii: 10.1038/s41467-020-18173-6
pmc: PMC7455706
doi:
Substances chimiques
Nuclear Proteins
0
Receptors, Neuropeptide Y
0
SUPT5H protein, human
0
Transcriptional Elongation Factors
0
neuropeptide Y4 receptor
55F8T1GN3X
Positive Transcriptional Elongation Factor B
EC 2.7.11.-
CDK9 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 9
EC 2.7.11.22
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4338Subventions
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM127289
Pays : United States
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