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Intergrated epigenetics, transcriptomics and metabolomics to analyze the mechanism of Benzo[a]pyrene neurotoxicity in hippocampus

ABSTRACT: Purpose: The aim of the study was to investigate the global effect of B[a]P on DNA methylation, non-coding RNAs (ncRNAs) and coding RNAs expression in the rat hippocampus. Methods: High-throughput sequencing was applied to assess hippocampus DNA methylation, ncRNAs and coding RNAs expression. Results: Exposure to B[a]P could influence the levels of DNA methylation, and the expression profiles of ncRNAs and mRNAs in rats. Conclusions: B[a]P could bring on the epigenetics changes as well as the transcriptomics changes and further affected gene expression.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE109973 | GEO | 2020/02/21

REPOSITORIES: GEO

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Project description:The general role of RNA in the cell beyond protein biosynthesis is only beginning to emerge with little knowledge about the structural or organizational functions of RNA. In turn, functional non-coding RNAs (ncRNAs) are often identified by their regulation or impact on cellular phenotypes. However, the huge number and diversity of ncRNAs highly complicate the task of their molecular characterization and rationalization into cellular processes. For the vast majority of ncRNAs as well as for non-coding functions of known mRNAs, the mechanisms underlying their modes of action as well as their impact on protein complexes are unknown. Thus, the greatest challenge in the field of RNA biology today is the elucidation of molecular mechanisms and functional interaction partners of RNA molecules. Since RNAs do not act alone, but often interact with specific protein partners, proteomic approaches have been developed to study RNA-binding proteins (RBPs) and aim at revealing the molecular mechanisms underlying RNA function. Large-scale studies aiming at globally identifying RNA-binding proteins principally focused on poly(A)-RNA transcripts. A notable limitation of such approaches is that many ncRNAs are not polyadenylated, so that their interaction partners were not detected in these screens. Most importantly however, the overlap between the numerous studies aiming to identify RBPs is limited and their specificity remains unclear. Moreover, the previous studies were based on the identification of RBPs omitting their participation in protein-protein complexes and more interestingly in RNA-dependent protein-protein complexes. Here, we introduce the concept of "RNA dependence" to overcome these challenges. We define a protein as RNA-dependent if its interactome (hence likely its function) depends on RNA without necessarily directly binding to RNA. Based on this new concept, we developed a proteome-wide screening approach to gain mechanistic insight into the function of RNAs - both coding and non-coding - in RNA-protein complexes and their impact on the function of such complexes.

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Intergrated epigenetics, transcriptomics and metabolomics to analyze the mechanism of Benzo[a]pyrene neurotoxicity in hippocampus

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