Assembly mechanism of Integrator's RNA cleavage module.
BRAT1
Galloway-Mowat Syndrome
NEDCAS
RNA polymerase II transcription
WDR73
inositol hexaphosphate
lethal neonatal rigidity and multifocal seizure syndrome
non-coding RNA processing
transcription attenuation
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
16 Jul 2024
16 Jul 2024
Historique:
received:
06
11
2023
revised:
17
05
2024
accepted:
26
06
2024
medline:
21
7
2024
pubmed:
21
7
2024
entrez:
20
7
2024
Statut:
aheadofprint
Résumé
The modular Integrator complex is a transcription regulator that is essential for embryonic development. It attenuates coding gene expression via premature transcription termination and performs 3'-processing of non-coding RNAs. For both activities, Integrator requires endonuclease activity that is harbored by an RNA cleavage module consisting of INTS4-9-11. How correct assembly of Integrator modules is achieved remains unknown. Here, we show that BRAT1 and WDR73 are critical biogenesis factors for the human cleavage module. They maintain INTS9-11 inactive during maturation by physically blocking the endonuclease active site and prevent premature INTS4 association. Furthermore, BRAT1 facilitates import of INTS9-11 into the nucleus, where it is joined by INTS4. Final BRAT1 release requires locking of the mature cleavage module conformation by inositol hexaphosphate (IP
Identifiants
pubmed: 39032489
pii: S1097-2765(24)00539-2
doi: 10.1016/j.molcel.2024.06.032
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.