ArticlePloS one2013
Paraquat modulates alternative pre-mRNA splicing by modifying the intracellular distribution of SRPK2.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- A meta-analysis of public microarray data identifies biological regulatory networks in Parkinson's disease.BMC medical genomics · 2018Pooled it
- Genome-scale analysis of Arabidopsis splicing-related protein kinase families reveals roles in abiotic stress adaptation.BMC plant biology · 2022Article
- Protective role of green tea against paraquat toxicity in Allium cepa L.: physiological, cytogenetic, biochemical, and anatomical assessment.Environmental science and pollution research international · 2022Article
- Hydrogen peroxide-induced stress acclimation in plants.Cellular and molecular life sciences : CMLS · 2022Review
- Good Cop, Bad Cop: The Different Roles of SRPKs.Frontiers in genetics · 2022Review
- Nuclear Translocation of SRPKs Is Associated with 5-FU and Cisplatin Sensitivity in HeLa and T24 Cells.Cells · 2021Article
- Inhalation of ZnO Nanoparticles: Splice Junction Expression and Alternative Splicing in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.The pharmacogenomics journal · 2017Article
- In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin.Molecular therapy. Nucleic acids · 2015Article
- The RNA Splicing Response to DNA Damage.Biomolecules · 2015Review
- Global variability in gene expression and alternative splicing is modulated by mitochondrial content.Genome research · 2015Article
- RNA splicing: a new player in the DNA damage response.International journal of cell biology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Paraquat (PQ) is a neurotoxic herbicide that induces superoxide formation. Although it is known that its toxic properties are linked to ROS production, the cellular response to PQ is still poorly understood. We reported previously that treatment with PQ induced genome-wide changes in pre-mRNA splicing. Here, we investigated the molecular mechanism underlying PQ-induced pre-mRNA splicing alterations. We show that PQ treatment leads to the phosphorylation and nuclear accumulation of SRPK2, a member of the family of serine/arginine (SR) protein-specific kinases. Concomitantly, we observed increased phosphorylation of SR proteins. Site-specific mutagenesis identified a single serine residue that is necessary and sufficient for nuclear localization of SRPK2. Transfection of a phosphomimetic mutant modified splice site selection of the E1A minigene splicing reporter similar to PQ-treatment. Finally, we found that PQ induces DNA damage and vice versa that genotoxic treatments are also able to promote SRPK2 phosphorylation and nuclear localization. Consistent with these observations, treatment with PQ, cisplatin or γ-radiation promote changes in the splicing pattern of genes involved in DNA repair, cell cycle control, and apoptosis. Altogether, our findings reveal a novel regulatory mechanism that connects PQ to the DNA damage response and to the modulation of alternative splicing via SRPK2 phosphorylation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.