Structural basis of Integrator-mediated transcription regulation.
Cryoelectron Microscopy
DNA-Binding Proteins
/ chemistry
Endoribonucleases
/ chemistry
Gene Expression Regulation
Humans
Models, Molecular
Multiprotein Complexes
/ chemistry
Protein Binding
Protein Conformation
Protein Domains
Protein Phosphatase 2
/ chemistry
Protein Subunits
/ chemistry
RNA
/ metabolism
RNA Polymerase II
/ chemistry
Transcription, Genetic
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
12 Nov 2021
12 Nov 2021
Historique:
entrez:
11
11
2021
pubmed:
12
11
2021
medline:
20
11
2021
Statut:
ppublish
Résumé
Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.
Identifiants
pubmed: 34762484
doi: 10.1126/science.abk0154
doi:
Substances chimiques
DNA-Binding Proteins
0
Multiprotein Complexes
0
Protein Subunits
0
RNA
63231-63-0
RNA Polymerase II
EC 2.7.7.-
Endoribonucleases
EC 3.1.-
INTS11 protein, human
EC 3.1.27
Protein Phosphatase 2
EC 3.1.3.16
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM