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

Evelyn Smit, Florian Caiment, Jolanda Piepers, Jos C. S. Kleinjans, Twan van den Beucken*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

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 mu M 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.

Original languageEnglish
Pages (from-to)144-152
Number of pages9
JournalToxicology Letters
Volume295
DOIs
Publication statusPublished - 1 Oct 2018

Keywords

  • mRNA translation
  • Benzo[a]pyrene
  • RNAseq
  • polysome fractionation
  • EXISTING MESSENGER-RNAS
  • LARGE GENE LISTS
  • ENDOPLASMIC-RETICULUM
  • EXPRESSION
  • TRANSCRIPTOMICS
  • CELLS
  • RECRUITMENT
  • POLYSOMES
  • HYPOXIA
  • CANCER

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