SRSF9 Regulates Cassette Exon Splicing of Caspase-2 by Interacting with Its Downstream Exon.
SRSF9
alternative splicing
caspase 2
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
19 03 2021
19 03 2021
Historique:
received:
08
02
2021
revised:
01
03
2021
accepted:
16
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
25
2
2023
Statut:
epublish
Résumé
Alternative splicing (AS) is an important posttranscriptional regulatory process. Damaged or unnecessary cells need to be removed though apoptosis to maintain physiological processes. Caspase-2 pre-mRNA produces pro-apoptotic long mRNA and anti-apoptotic short mRNA isoforms through AS. How AS of Caspase-2 is regulated remains unclear. In the present study, we identified a novel regulatory protein SRSF9 for AS of Caspase-2 cassette exon 9. Knock-down (KD) of SRSF9 increased inclusion of cassette exon and on the other hand, overexpression of SRSF9 decreased inclusion of this exon. Deletion mutagenesis demonstrated that exon 9, parts of intron 9, exon 8 and exon 10 were not required for the role of SRSF9 in Caspase-2 AS. However, deletion and substitution mutation analysis revealed that AGGAG sequence located at exon 10 provided functional target for SRSF9. In addition, RNA-pulldown mediated immunoblotting analysis showed that SRSF9 interacted with this sequence. Gene ontology analysis of RNA-seq from SRSF9 KD cells demonstrates that SRSF9 could regulate AS of a subset of apoptosis related genes. Collectively, our results reveal a basis for regulation of Caspase-2 AS.
Identifiants
pubmed: 33808656
pii: cells10030679
doi: 10.3390/cells10030679
pmc: PMC8003524
pii:
doi:
Substances chimiques
RNA Precursors
0
RNA-Binding Proteins
0
SRSF9 protein, human
0
Transcription Factors
0
Serine-Arginine Splicing Factors
170974-22-8
Caspase 2
EC 3.4.22.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the Ministry of Education and the National Research Foundation of Korea
ID : 2020R1A2C2004682
Organisme : the Ministry of Education and the National Research Foundation of Korea
ID : 2019R1I1A1A01057372
Organisme : the Ministry of Education and the National Research Foundation of Korea
ID : 2016R1A5A1007318
Organisme : the Associazione Italiana per la Ricerca sul Cancro
ID : IG 2018 Id.21966
Organisme : GIST Research Institute (GRI) IIBR
ID : 2021
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