Decreased translation of Dio3 mRNA is associated with drug-induced hepatotoxicity.

ABSTRACT: Recent work has demonstrated the importance of post-transcriptional gene regulation in toxic responses. In the present study, we used two rat models to investigate mRNA translation in the liver following xenobiotic-induced toxicity. By combining polysome profiling with genomic methodologies, we were able to assess global changes in hepatic mRNA translation. Dio3 (iodothyronine deiodinase type III) was identified as a gene that exhibited specific translational repression and had a functional role in a number of relevant canonical pathways. Western blot analysis indicated that this repression led to reduced D3 (the protein expressed by Dio3) levels, enhanced over time and with increased dose. Using Northern blotting techniques and qRT-PCR (quantitative reverse transcription-PCR), we confirme

SUBMITTER: Dudek KM 

PROVIDER: S-EPMC3682751 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature