Functional Network Analysis Reveals the Relevance of SKIIP in the Regulation of Alternative Splicing by p38 SAPK.
Alternative Splicing
/ drug effects
Cell Cycle Proteins
/ genetics
HeLa Cells
Humans
Imidazoles
/ pharmacology
MAP Kinase Kinase 6
/ metabolism
Nuclear Receptor Coactivators
/ antagonists & inhibitors
Osmotic Pressure
Phosphorylation
Protein Isoforms
/ genetics
Protein Serine-Threonine Kinases
/ genetics
Protein-Tyrosine Kinases
/ genetics
Pyridines
/ pharmacology
RNA Interference
RNA, Small Interfering
/ metabolism
Sodium Chloride
/ pharmacology
p38 Mitogen-Activated Protein Kinases
/ metabolism
Dyrk Kinases
GADD45
alternative splicing
cell signaling
p38 SAPK
stress responses
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 04 2019
16 04 2019
Historique:
received:
03
09
2018
revised:
21
02
2019
accepted:
15
03
2019
entrez:
18
4
2019
pubmed:
18
4
2019
medline:
17
6
2020
Statut:
ppublish
Résumé
Alternative splicing is a prevalent mechanism of gene regulation that is modulated in response to a wide range of extracellular stimuli. Stress-activated protein kinases (SAPKs) play a key role in controlling several steps of mRNA biogenesis. Here, we show that osmostress has an impact on the regulation of alternative splicing (AS), which is partly mediated through the action of p38 SAPK. Splicing network analysis revealed a functional connection between p38 and the spliceosome component SKIIP, whose depletion abolished a significant fraction of p38-mediated AS changes. Importantly, p38 interacted with and directly phosphorylated SKIIP, thereby altering its activity. SKIIP phosphorylation regulated AS of GADD45α, the upstream activator of the p38 pathway, uncovering a negative feedback loop involving AS regulation. Our data reveal mechanisms and targets of SAPK function in stress adaptation through the regulation of AS.
Identifiants
pubmed: 30995481
pii: S2211-1247(19)30390-0
doi: 10.1016/j.celrep.2019.03.060
pmc: PMC6484779
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
GADD45A protein, human
0
Imidazoles
0
Nuclear Receptor Coactivators
0
Protein Isoforms
0
Pyridines
0
RNA, Small Interfering
0
SNW1 protein, human
0
Sodium Chloride
451W47IQ8X
Protein-Tyrosine Kinases
EC 2.7.10.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
MAP Kinase Kinase 6
EC 2.7.12.2
MAP2K6 protein, human
EC 2.7.12.2
SB 203580
OU13V1EYWQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
847-859.e6Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
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