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mRNA Quality Control Is Activated Due To Chromium (VI) Mediated Oxidative Damage
Author(s) -
GarciaDoherty Naiara,
Larson Abbi L,
Six Marshall,
Segal Scott P
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.599.1
Subject(s) - nonsense mediated decay , messenger rna , chemistry , microbiology and biotechnology , translation (biology) , gene , biology , biochemistry , rna , rna splicing
Chromium VI (Cr(VI)) is a genotoxic stressor that is known to cause 8‐oxoG bases to form in DNA. However, little is known regarding whether Cr(VI) has an effect directly at the level of mRNA. Prior data showed that treatment with Cr(VI) results in the selective assembly of P‐bodies, but not stress granules. This selective P‐body assembly requires translational repression to occur. This leads to a model in which mRNA either transcribed from damaged genes, or mRNA damaged directly by the Cr(VI) is sent to P‐bodies for degradation. To test between these two possibilities, strains in which transcription has been repressed by actinomycin D were subsequently treated with Cr(VI). Upon the dual treatment, P‐body assembly was unaffected, suggesting that Cr(VI) may have the ability to damage mRNA, and it is these mRNA that are, in turn, be localized to P‐bodies. Several mRNA quality control pathways exist in eukaryotes that potentially shuttle mRNA through P‐bodies for subsequent degradation. Of significance, are the Nonsense Mediated Decay (NMD) pathway, which degrades mRNA with premature termination codons, and the No‐Go pathway, which degrades mRNA in which ribosomes have stalled during translation. To test which pathway(s) may be activated in response to Cr(VI), deletion mutants were used to reduce or eliminate the activity of specific pathways. Upon reduction of NMD activity, no effect on P‐body assembly was seen in response to Cr(VI). However, reducing No‐Go decay, resulted in a significant reduction in P‐body assembly. Based on this data, it is likely that the increase in P‐body assembly through Cr(VI) can directly damage mRNA. This could potentially lead to stalled ribosomes during translation and subsequent activation of the No‐Go decay pathway.