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Determining the Physiological Basis of No‐Go Decay Using sod1Δ Strains in Saccharomycescerevisiae
Author(s) -
Lobb Amber,
Cianflone Emily,
Champine Madison,
Bailey Lindsey,
Seaberg Lucas,
Segal Scott P
Publication year - 2019
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.2019.33.1_supplement.629.4
Subject(s) - sod1 , chemistry , ribosome , oxidative stress , superoxide dismutase , microbiology and biotechnology , biophysics , mutant , biochemistry , oxidative phosphorylation , superoxide , gene , biology , enzyme , rna
Chromium VI (Cr(VI)) induces oxidative stress in cells, resulting in altered gene expression, increased apoptosis and cell death. Previous work showed that Cr(VI) exposure results in the formation of 8‐oxo(G) bases in mRNA. The presence of 8‐oxo(G) bases can lead to ribosome stalls during translation and activation of no‐go decay. During no‐go decay, the Dom34p/Hbsp1p complex acts to remove stalled ribosomes and subsequent endonucleolytic cleavage of the damaged mRNA at the stall site. Although oxidative agents and other non‐physiological substrates have been used to activate no‐go decay, very little work exists to elucidate the true physiological role of this pathway. Sod1p (superoxide dismutase 1) acts to scavenge free oxygen species by catalyzing the partitioning of superoxide (O 2 − ) into O 2 and H 2 O 2 . Cells that lack functional Sod1p were observed to have increased oxidative stress resulting in increased P‐body assembly. Yet, global translation was only attenuated. To determine whether no‐go decay is being activated in strains lacking Sod1p, double mutant strains were created in which SOD1 was knocked out in conjunction with one of the effectors of no‐go decay. Consistent with no‐go decay being activated in response to oxidation, the hbs 1Δsod1Δ strain resulted in a decrease in P‐body assembly, as compared to wild‐type, even in the presence of Cr (VI). Interestingly, Stm1p is thought to potentially to aid in the dissociation and recycling of the ribosomal subunits. In the stm1Δ strain, P‐body assembly was mildly decreased as compared to the wild‐type upon treatment with Cr(VI). This is consistent with Stm1p functioning to recycle ribosomes downstream of no‐go decay. Additionally, a stm1Δ can can suppress sod1Δ growth defects on Cr(VI) containing media. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .