Activation of human RNA lariat debranching enzyme Dbr1 by binding protein TTDN1 occurs though an intrinsically disordered C-terminal domain.
RNA
branched RNA
crystal structure
debranching enzyme
introns
lariats
metalloenzymes
metallophosphodiesterase
phosphorothioate
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
26
04
2023
revised:
11
07
2023
accepted:
20
07
2023
medline:
2
10
2023
pubmed:
29
7
2023
entrez:
28
7
2023
Statut:
ppublish
Résumé
In eukaryotic cells, the introns are excised from pre-mRNA by the spliceosome. These introns typically have a lariat configuration due to the 2'-5' phosphodiester bond between an internal branched residue and the 5' terminus of the RNA. The only enzyme known to selectively hydrolyze the 2'-5' linkage of these lariats is the RNA lariat debranching enzyme Dbr1. In humans, Dbr1 is involved in processes such as class-switch recombination of immunoglobulin genes, and its dysfunction is implicated in viral encephalitis, HIV, ALS, and cancer. However, mechanistic details of precisely how Dbr1 affects these processes are missing. Here we show that human Dbr1 contains a disordered C-terminal domain through sequence analysis and nuclear magnetic resonance. This domain stabilizes Dbr1 in vitro by reducing aggregation but is dispensable for debranching activity. We establish that Dbr1 requires Fe
Identifiants
pubmed: 37507019
pii: S0021-9258(23)02128-2
doi: 10.1016/j.jbc.2023.105100
pmc: PMC10470207
pii:
doi:
Substances chimiques
Dbr1 protein, human
EC 2.7.7.-
RNA Nucleotidyltransferases
EC 2.7.7.-
MPLKIP protein, human
0
Adaptor Proteins, Signal Transducing
0
Intrinsically Disordered Proteins
0
Metals, Heavy
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
105100Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM094157
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM105681
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127472
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare no conflict of interest with the contents of this article.