Abstract

Transcript levels are the primary factor determining protein levels, but for the majority of genes, fold changes in transcript levels are larger than the corresponding changes in protein levels, a phenomenon that is termed “protein homeostasis”. However, this phenomenon is not well characterized in the context of environmental changes. In this study, we sequenced the entire transcriptome and proteome of chicken primary hepatocytes administered three mycotoxin treatments Aflatoxin B1 (AFB1), Ochoratoxin A (OTA) and Zearalenone (ZEN). Each mycotoxin induced unique set of differential expressed transcripts and proteins, suggesting variable cytotoxicity and biochemical action in cell. We found a weak positive correlation between transcript and protein changes, and the transcript changes were higher than the protein changes. Furthermore, we observed pathway-specific protein homeostasis pattern under mycotoxin stress. Specifically, the “Metabolism”, “Transcription” and “Translation” pathways (housekeeping pathways) showed lower fold changes in protein/mRNA levels than non-housekeeping pathways such as “Cell growth and death” and “Immune system”. Protein molecular weight had a weak negative effect on protein production, and this effect was stronger for non-housekeeping pathways. Overall, we hypothesize housekeeping pathways maintain stable protein production for baseline cellular function, whereas non-housekeeping pathways is associated with the fitness response to environmental stress.

Highlights

  • The central dogma that the information flow in a biological system is generally from DNA to RNA to protein is the cornerstone of modern molecular biology

  • Chicken primary hepatocytes were administrated by three mycotoxins Aflatoxin B1 (AFB1), ochoratoxin A (OTA) and ZEN

  • We found some similarities between different mycotoxin administrations, such as “ECM-receptor interaction” pathways were enriched with down-regulated proteins for both AFB1 and OTA, the overall distribution of differentially expressed transcripts (DETs) and differentially expressed proteins (DEPs) was quite different for the three mycotoxins

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Summary

Introduction

The central dogma that the information flow in a biological system is generally from DNA to RNA to protein is the cornerstone of modern molecular biology. Recent observations from fission yeast, human tumors and evolutionary studies between humans and chimpanzees, revealed that fold changes in mRNA levels are generally larger than fold changes in protein levels[10,11,12] This phenomenon is termed as protein homeostasis that protein production is maintained at a stable level in the cell despite fluctuations in mRNA1. Aflatoxin B1 (AFB1), OTA and ZEN are some of the most widely spread mycotoxins in the world Previous studies reported these mycotoxins have similar toxic actions in cells including prohibiting RNA and protein synthesize, DNA damage and ROS13,18,19, but none of them quantified the expression profile at the omics level. Genes from different pathways showed differing levels of protein homeostasis, indicating protein homeostasis was primarily maintained by housekeeping pathways in the cell

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