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Spliceostatin A interaction with SF3B limits U1 snRNP availability and causes premature cleavage and polyadenylation
- Source :
- Cell chemical biology. 28(9)
- Publication Year :
- 2020
-
Abstract
- RNA splicing, a highly conserved process in eukaryotic gene expression, is seen as a promising target for anticancer agents. Splicing is associated with other RNA processing steps, such as transcription and nuclear export; however, our understanding of the interaction between splicing and other RNA regulatory mechanisms remains incomplete. Moreover, the impact of chemical splicing inhibition on long non-coding RNAs (lncRNAs) has been poorly understood. Here, we demonstrate that spliceostatin A (SSA), a chemical splicing modulator that binds to the SF3B subcomplex of the U2 small nuclear ribonucleoprotein particle (snRNP), limits U1 snRNP availability in splicing, resulting in premature cleavage and polyadenylation of MALAT1, a nuclear lncRNA, as well as protein-coding mRNAs. Therefore, truncated transcripts are exported into the cytoplasm and translated, resulting in aberrant protein products. Our work demonstrates that active recycling of the splicing machinery maintains homeostasis of RNA processing beyond intron excision.
- Subjects :
- Polyadenylation
RNA Splicing
Clinical Biochemistry
Biology
Biochemistry
Ribonucleoprotein, U1 Small Nuclear
Drug Discovery
Gene expression
Tumor Cells, Cultured
Humans
snRNP
Spiro Compounds
Nuclear export signal
Molecular Biology
Pyrans
Pharmacology
Small Nuclear Ribonucleoprotein Particle
Intron
RNA
Phosphoproteins
Cell biology
RNA splicing
Molecular Medicine
Female
RNA, Long Noncoding
RNA Splicing Factors
HeLa Cells
Subjects
Details
- ISSN :
- 24519448
- Volume :
- 28
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Cell chemical biology
- Accession number :
- edsair.doi.dedup.....268ecdfb71d73a14ceff392d5fff0a63