Poster abstracts

Poster number 64 submitted by Raul Jobava

Novel functions of cytochrome C in the cellular response to stress

Raul Jobava (Department of Biochemistry, Case Western Reserve University, Cleveland, OH ), Mridusmita Saikia (Department of Pharmacology, Case Western Reserve University, Cleveland, OH ), Andrea Putnam (RNA Center/Department of Biochemistry, Case Western Reserve University, Cleveland, OH ), Tao Pan (Department of Biochemistry and Biophysics, University of Chicago, Chicago, IL), Eckhard Jankowsky (RNA Center/Department of Biochemistry, Case Western Reserve University, Cleveland, OH ), Maria Hatzoglou (Department of Pharmacology, Case Western Reserve University, Cleveland, OH )

Abstract:
Regulation of cell volume in response to changes of extracellular tonicity is essential for cell survival. Hyperosmotic stress is associated with inflammation, diabetes and other diseases. Severe hyperosmotic stress induces cytochrome C release from the mitochondria, formation of the apoptosome and initiation of apoptosis. Hyperosmotic stress also activates the ribonuclease Angiogenin, which cleaves a small pool of tRNAs in the anticodon loop producing 30-45 nt long half tRNA molecules known as tiRNAs (tRNA-derived stress-induced fragments). The subcellular localization and molecular function of these small RNAs is largely unknown. Here we demonstrate that certain tiRNAs bind cytochrome C in the cytoplasm after it is released from mitochondria. Next generation sequencing revealed that twenty tiRNAs are highly enriched in this cytochrome C ribonucleoprotein complex. Direct binding of cytochrome C to tiRNAs within the cytochrome C ribonucleoprotein complex was confirmed using RNA gel-shift analysis. Our preliminary data suggest, that certain tiRNAs have prosurvival functions during hyperosmotic stress by inhibiting apoptosome formation. Our findings also reveal novel functions of cytochrome C during hyperosmotic stress which can be further explored for therapeutic purposes of protecting healthy cells from apoptosis.

Keywords: tiRNA, cytochrome C, stress