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Toxicol Lett. 2018 Oct 1;295:144-152. doi: 10.1016/j.toxlet.2018.06.009. Epub 2018 Jun 12.

Translational regulation is a key determinant of the cellular response to benzo[a]pyrene.

Author information

1
Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, 6200MD, The Netherlands.
2
Department of Toxicogenomics, GROW School for Oncology and Developmental Biology, Maastricht University, Maastricht, 6200MD, The Netherlands. Electronic address: t.vandenbeucken@maastrichtuniversity.nl.

Abstract

Translational control is a cellular response mechanism which initiates adaptation during various stress situations. Here, we investigated the role of translational control after benzo[a]pyrene (BaP) exposure in primary mouse hepatocytes. Translated mRNAs were separated and captured based on the number of associated ribosomes using sucrose gradients and subjected to RNA sequencing (RNAseq) to investigate translational changes. Furthermore, unseparated RNA (total RNA) was used for RNAseq to determine the transcriptional alterations. We showed that, after 24 h of exposure to 10 μM BaP, the number of genes altered by changes in mRNA translation was substantially higher compared with the number of genes altered by transcription. Although part of the BaP regulated genes were regulated by both transcription and translation, we identified genes that were uniquely regulated by mRNA translation. These mRNA transcripts encode proteins that are involved in biological processes that are not affected by transcriptional regulation. Al together this work identified a new layer of gene expression regulation that might contribute to BaP-induced carcinogenesis.

KEYWORDS:

Benzo[a]pyrene; RNAseq; mRNA translation; polysome fractionation

PMID:
29906497
DOI:
10.1016/j.toxlet.2018.06.009
[Indexed for MEDLINE]

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