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The regulation of apoptosis by RNA processing factors in Saccharomyces cerevisiae (762.4)
Author(s) -
Chirigos Allison,
Schwotzer Erica,
Luo Yi,
Whitworth Gregg
Publication year - 2014
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.28.1_supplement.762.4
Subject(s) - saccharomyces cerevisiae , phosphorylation , serine , microbiology and biotechnology , context (archaeology) , mutant , apoptosis , biology , messenger rna , chemistry , yeast , biochemistry , gene , paleontology
We have identified a novel link between mRNA processing and the regulation of apoptosis in the yeast Saccharomyces cerevisiae: the mRNA export factor Npl3, and its cytoplasmic kinase Sky1, are both necessary for the induction of apoptosis in response to environmental stress conditions. In the normal nuclear export cycle, Sky1 phoshorylation of serine 411 in the RS domain of Npl3 is associated with cytoplasmic release of the mRNA cargo. Provocatively, deletion of either factor (sky1Δ, npl3Δ), or mutation of the phosphorylation site (npl3‐S411A), abrogates induction of apoptosis in response to cation toxicity (CuSO 4 , LiCl). We are currently using HPLC‐coupled mass spectroscopy to quantify Npl3 phosphorylation levels at both the canonical site and adjacent residues which have been suggested as possible phosphorylation targets by high‐throughput mass spectrometry sequencing. Additionally, we are using high‐throughput epistatic‐analysis of double mutants to construct a genetic interaction network which probes the role of NPL3 and SKY1 in apoptotic stress conditions in the context of well described regulators of both the metacaspase‐mediated (YCA1) and mitochondrial (AIF1) pathways. In total, our data suggest a role for the Npl3/Sky1 export machinery in the mitochondrial pathway. Grant Funding Source : EJS, AJC, YL & GW supported by the HHMI Fellows Program & Grant Initiative; GW by Lenfest Grants.