KDM3A regulates alternative splicing of cell-cycle genes following DNA damage.
Acetyltransferases
/ genetics
Alternative Splicing
Breast Neoplasms
/ genetics
DNA Damage
DNA-Binding Proteins
/ genetics
Gene Expression Regulation, Neoplastic
Humans
Jumonji Domain-Containing Histone Demethylases
/ genetics
MCF-7 Cells
Phosphorylation
Protein Binding
RNA Precursors
/ genetics
Serine-Arginine Splicing Factors
/ genetics
Transcription Factors
/ genetics
alternative splicing
chromatin
pre-mRNA splicing
Journal
RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
13
04
2021
accepted:
26
07
2021
pubmed:
30
7
2021
medline:
15
12
2021
entrez:
29
7
2021
Statut:
ppublish
Résumé
Changes in the cellular environment result in chromatin structure alteration, which in turn regulates gene expression. To learn about the effect of the cellular environment on the transcriptome, we studied the H3K9 demethylase KDM3A. Using RNA-seq, we found that KDM3A regulates the transcription and alternative splicing of genes associated with cell cycle and DNA damage. We showed that KDM3A undergoes phosphorylation by PKA at serine 265 following DNA damage, and that the phosphorylation is important for proper cell-cycle regulation. We demonstrated that SAT1 alternative splicing, regulated by KDM3A, plays a role in cell-cycle regulation. Furthermore we found that KDM3A's demethylase activity is not needed for SAT1 alternative splicing regulation. In addition, we identified KDM3A's protein partner ARID1A, the SWI/SNF subunit, and SRSF3 as regulators of SAT1 alternative splicing and showed that KDM3A is essential for SRSF3 binding to SAT1 pre-mRNA. These results suggest that KDM3A serves as a sensor of the environment and an adaptor for splicing factor binding. Our work reveals chromatin sensing of the environment in the regulation of alternative splicing.
Identifiants
pubmed: 34321328
pii: rna.078796.121
doi: 10.1261/rna.078796.121
pmc: PMC8522690
doi:
Substances chimiques
ARID1A protein, human
0
DNA-Binding Proteins
0
RNA Precursors
0
SRSF3 protein, human
0
Transcription Factors
0
Serine-Arginine Splicing Factors
170974-22-8
Jumonji Domain-Containing Histone Demethylases
EC 1.14.11.-
KDM3A protein, human
EC 1.14.11.-
Acetyltransferases
EC 2.3.1.-
diamine N-acetyltransferase
EC 2.3.1.57
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1353-1362Informations de copyright
© 2021 Baker et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.
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