Stress-induced nuclear speckle reorganization is linked to activation of immediate early gene splicing.
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
04 12 2023
04 12 2023
Historique:
received:
30
11
2021
revised:
13
07
2023
accepted:
29
09
2023
pmc-release:
13
05
2024
medline:
15
11
2023
pubmed:
13
11
2023
entrez:
13
11
2023
Statut:
ppublish
Résumé
Current models posit that nuclear speckles (NSs) serve as reservoirs of splicing factors and facilitate posttranscriptional mRNA processing. Here, we discovered that ribotoxic stress induces a profound reorganization of NSs with enhanced recruitment of factors required for splice-site recognition, including the RNA-binding protein TIAR, U1 snRNP proteins and U2-associated factor 65, as well as serine 2 phosphorylated RNA polymerase II. NS reorganization relies on the stress-activated p38 mitogen-activated protein kinase (MAPK) pathway and coincides with splicing activation of both pre-existing and newly synthesized pre-mRNAs. In particular, ribotoxic stress causes targeted excision of retained introns from pre-mRNAs of immediate early genes (IEGs), whose transcription is induced during the stress response. Importantly, enhanced splicing of the IEGs ZFP36 and FOS is accompanied by relocalization of the corresponding nuclear mRNA foci to NSs. Our study reveals NSs as a dynamic compartment that is remodeled under stress conditions, whereby NSs appear to become sites of IEG transcription and efficient cotranscriptional splicing.
Identifiants
pubmed: 37956386
pii: 276406
doi: 10.1083/jcb.202111151
pmc: PMC10641589
pii:
doi:
Substances chimiques
Ribonucleoprotein, U1 Small Nuclear
0
RNA Precursors
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Sung et al.
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