Regulated capture by exosomes of mRNAs for cytoplasmic tRNA synthetases

Abstract

Although tRNA synthetases are enzymes that catalyze the first step of translation in the cytoplasm, surprising functions unrelated to translation have been reported. These studies, and the demonstration of novel activities of splice variants, suggest a far broader reach oftRNAsynthetases into cell biology than previously recognized. Here we show thatmRNAsfor most tRNA synthetases can be detected in exosomes. Also detected in exosomes was an mRNAencoding a unique splice variant that others had associated with prostate cancer. The exosomal mRNAs encoding the native synthetase and its cancer-associated splice variant could be translated in vitro and in mammalian cells into stable proteins. Other results showed that selection by exosomes of the splice variant mRNA could be regulated by an external stimulus. Thus, a broad and diverse regulated pool of tRNA synthetase-derived mRNAs is packaged for genetic exchange. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.