Precursor of pro-apoptotic cytokine modulates aminoacylation activity of tRNA synthetase

Abstract

Endothelial monocyte activating polypeptide II (EMAPII) is a cytokine that is specifically induced by apoptosis. Its precursor (pro-EMAPII) has been suggested to be identical to p43, which is associated with the multi- tRNA synthetase complex. Herein, we have demonstrated that the N-terminal domain of pro-EMAPH interacts with the N-terminal extension of human cytoplasmic arginyl-tRNA synthetase (RRS) using genetic and immunoprecipitation analyses. Aminoacylation activity of RRS was enhanced about 2.5-fold by the interaction with pro-EMAPH but not with its N- or C- terminal domains alone. The N-terminal extension of RRS was not required for enzyme activity but did mediate activity stimulation by pro-EMAPH. Pro-EMAPH reduced the apparent K(m) of RRS to tRNA, whereas the k(cat) value remained unchanged. Therefore, the precursor of EMAPII is a multi-functional protein that assists aminoacylation in normal cells and releases the functional cytokine upon apoptosis.