Abstract
Gamma radiation produces DNA instability and impaired phenotype. Previously, we observed negative effects on phenotype, DNA methylation, and gene expression profiles, in offspring of zebrafish exposed to gamma radiation during gametogenesis. We hypothesize that previously observed effects are accompanied with changes in the expression profile of non-coding RNAs, inherited by next generations. Non-coding RNA expression profile was analysed in F1 offspring (5.5 h post-fertilization) by high-throughput sequencing 1 year after parental irradiation (8.7 mGy/h, 5.2 Gy total dose). Using our previous F1-γ genome-wide gene expression data (GSE98539), hundreds of mRNAs were predicted as targets of differentially expressed (DE) miRNAs, involved in pathways such as insulin receptor, NFkB and PTEN signalling, linking to apoptosis and cancer. snRNAs belonging to the five major spliceosomal snRNAs were down-regulated in the F1-γ group, Indicating transcriptional and post-transcriptional alterations. In addition, DEpiRNA clusters were associated to 9 transposable elements (TEs) (LTR, LINE, and TIR) (p = 0.0024), probable as a response to the activation of these TEs. Moreover, the expression of the lincRNAs malat-1, and several others was altered in the offspring F1, in concordance with previously observed phenotypical alterations. In conclusion, our results demonstrate diverse gamma radiation-induced alterations in the ncRNA profiles of F1 offspring observable 1 year after parental irradiation.
Highlights
Ionizing radiation can induce direct or indirect DNA damages, causing single or double-stranded breaks, or ionization of water resulting in the formation of free radicals
The DNA methylation analysis along with the mRNA expression profile of F 1 embryos revealed pathways associated with gamma radiation response; such as molecular mechanisms of cancer, DNA damage response and cell death, along with pathways not previously seem involved in the response to gamma radiation, like signalling and retinoic acid receptor activation, and gonadotropin-releasing hormone (Gnrh) signalling
We have focused on small non-coding RNAs (sncRNAs) expression through small RNA-seq to analyse the sncRNA profile in 5.5 hpf F1 offspring embryos 1 year after parental exposure to gamma radiation (8.7 mGy/h) during gametogenesis
Summary
Ionizing radiation can induce direct or indirect DNA damages, causing single or double-stranded breaks, or ionization of water resulting in the formation of free radicals. The cell response cascade to gamma radiation includes changes in gene expression through epigenetic modifications such as post-translational histone modifications, DNA methylation, and microRNAs (miRNAs) such as the oncomir miR-212–4. Gamma radiation-induced alterations at transcriptional, and DNA level can be inherited by the offspring of vertebrates. We recently demonstrated the inheritance of altered mRNA expression profiles, DNA methylation, and histone modifications patterns in zebrafish embryos after parental gamma irradiation[8,9,10]. The inheritance of dysregulated profiles for most of the sncRNA classes in zebrafish offspring, as well as their involvement in the mechanisms underlying the response to gamma radiation, as a result of parental exposure, remains unclear
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