SRSF1 Is a Mediator of Radiation-Induced Alternative Splicing in B-Lymphocytes
| العنوان: | SRSF1 Is a Mediator of Radiation-Induced Alternative Splicing in B-Lymphocytes |
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| المؤلفون: | Vivian G. Cheung, Niema Razavian |
| المصدر: | Blood. 128:1341-1341 |
| بيانات النشر: | American Society of Hematology, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Immunology, Alternative splicing, Intron, RNA, Cell Biology, Hematology, Biology, Biochemistry, Exon skipping, Splicing factor, Exon, RNA splicing, Cancer research, Gene |
| الوصف: | Ionizing radiation is used in the treatment of Hodgkin and non-Hodgkin lymphomas (Spetch et al. 2014; Illidge et al. 2014). Despite its effectiveness, radiation is a "blunt" therapy that damages indiscriminately both cancer and normal cells, and can result in secondary malignancies (Dores et al. 2002). To better understand cellular response to radiation, we examined alternative splicing, and its regulation, in irradiated human cells. To accomplish this, we exposed cultured B-lymphocytes from 10 individuals to 10 Gy of ionizing radiation, and performed RNA sequencing before, and two and six hours after radiation treatment. With these data, we first identified alternative splicing events. From about 60 million reads per sample, we detected over 20,000 alternatively spliced events. In total, 1,600 events were radiation responsive (ANOVA, FDR Next, we looked for how alternative splicing is regulated in response to radiation. To identify putative mediators of this response, we determined the expression levels of over 60 trans-acting splicing factors. We found that the expression level of 26 splicing factors changed significantly in irradiated cells (ANOVA, FDR Finally, we examined the link between SRSF1 and exon skipping in irradiated cells more closely. For example, in the transcripts for RNA-binding protein 3 (RBM3), SRSF1 binds an RBM3 exon that contains a premature termination codon (Sanford et al. 2009), and mediates exclusion of this exon. We confirmed experimentally that this results in an increase in RBM3 protein expression. Together, our data demonstrate that alternative splicing is a key part of cellular response to radiation, and SRSF1 plays a role in mediating exon skipping. In this presentation, we will describe radiation-induced alternative splicing by discussing the genes that are alternatively spliced, and its regulation by the splicing factor SRSF1. Disclosures No relevant conflicts of interest to declare. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::3dba0b79354dc9cec17f43ca76d1c01c https://doi.org/10.1182/blood.v128.22.1341.1341 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........3dba0b79354dc9cec17f43ca76d1c01c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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