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Evolving from an enzyme and into a regulator
Proteins, the work-horses of the cell, are made on a messenger RNA (mRNA) template. An enzyme called aminoacyl tRNA synthetases (AARSs) attaches the correct amino acid to a transfer RNA so that mRNA is accurately translated. Over evolution, additional sequences have been added to AARSs. Lo et al. found a large number of AARS variants in which the domain responsible for enzyme function was deleted. Ninety-four such variants had diverse signaling activities. Thus, AARSs are used both as enzymes and alternately as regulators of signaling pathways.
Science, this issue p. 328
Abstract
Genetic efficiency in higher organisms depends on mechanisms to create multiple functions from single genes. To investigate this question for an enzyme family, we chose aminoacyl tRNA synthetases (AARSs). They are exceptional in their progressive and accretive proliferation of noncatalytic domains as the Tree of Life is ascended. Here we report discovery of a large number of natural catalytic nulls (CNs) for each human AARS. Splicing events retain noncatalytic domains while ablating the catalytic domain to create CNs with diverse functions. Each synthetase is converted into several new signaling proteins with biological activities “orthogonal” to that of the catalytic parent. We suggest that splice variants with nonenzymatic functions may be more general, as evidenced by recent findings of other catalytically inactive splice-variant enzymes.
