Studying the adaptive changes of transcript abundance or splice variants upon repeated stimulation by KCl-induced depolarization or by dopamine
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Date
2018
Authors
Ghandizadeh Dezfouli, Maryam
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Abstract
Objective: One of the key steps of the regulation of gene expression is alternative splicing of pre-mRNA. Previous studies have shown that alternative splicing is critical for adaptive changes of cells to repeated stimulation or stress. However, the underlying mechanisms of alternative splicing during these changes remain elusive. In this study we aim to identify the different effects of repeated versus single stimulation on the transcript abundance or alternative splicing of particular genes. Method: Effect of a single exposure or repeated dopamine (DA) or KCl treatment on the transcript abundance or alternative splicing of FosB in striatal cells was examined using RT-PCR. Moreover, to determine the changes of other candidate genes in this treatment scheme, RNA-Seq was carried out on the striatal cells treated with DA.
Results: While changes in splicing variants of FosB was evident after KCl or DA stimulation, there was no difference in changes observed after a single exposure or after repeated treatment with KCl or DA. RNA-Seq data showed that the splicing factor cluster of genes was the most significant group that changed in alternative splicing after repeated DA treatment compared with non-treated (NT) cells. The transcription factor cluster, was most significantly changed for splice variation after a single exposure to KCl or DA. A similar difference was seen between repeated exposure and single exposure condition. In addition, with respect to transcript abundance, there were unique signatures of gene clusters affected by either single exposure or repeated exposure treatment.
Conclusion: Alternative splicing of FosB does not change after repeated compared to first stimulation by KCl or DA. However, RNA-Seq reveals that repeated stimulation affects the expression, particularly alternative splicing of specific genes differently from that observed for a single stimulation.
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Keywords
Alternative Splicing, Dopamine, KCl-induced Depolarization, RNA-Seq, FosB