Translocation of a Cell Surface Spliceosomal Complex Induces Alternative Splicing Events and Lymphoma Cell Necrosis.
AP-MS
G-quadruplex
affinity labeling
alternative splicing
aptamer
cancer
non-Hodgkin’s lymphoma
ribonucleoproteins
spliceosome
Journal
Cell chemical biology
ISSN: 2451-9448
Titre abrégé: Cell Chem Biol
Pays: United States
ID NLM: 101676030
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
received:
22
10
2018
revised:
10
12
2018
accepted:
24
02
2019
pubmed:
2
4
2019
medline:
13
3
2020
entrez:
2
4
2019
Statut:
ppublish
Résumé
Spliceosomal dysregulation dramatically affects many cellular processes, notably signal transduction, metabolism, and proliferation, and has led to the concept of targeting intracellular spliceosomal proteins to combat cancer. Here we show that a subset of lymphoma cells displays a spliceosomal complex on their surface, which we term surface spliceosomal complex (SSC). The SSC consists of at least 13 core components and was discovered as the binding target of the non-Hodgkin's lymphoma-specific aptamer C10.36. The aptamer triggers SSC internalization, causing global changes in alternative splicing patterns that eventually lead to necrotic cell death. Our study reveals an exceptional spatial arrangement of a spliceosomal complex and defines it not only as a potential target of anti-cancer drugs, but also suggests that its localization plays a fundamental role in cell survival.
Identifiants
pubmed: 30930163
pii: S2451-9456(19)30071-6
doi: 10.1016/j.chembiol.2019.02.016
pii:
doi:
Substances chimiques
Aptamers, Nucleotide
0
Heterogeneous-Nuclear Ribonucleoprotein U
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
756-764.e6Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.