Human tRNA synthetase catalytic nulls with diverse functions.

Bibliographic Collection: 
Publication Type: Journal Article
Authors: Lo, Wing-Sze; Gardiner, Elisabeth; Xu, Zhiwen; Lau, Ching-Fun; Wang, Feng; Zhou, Jie J; Mendlein, John D; Nangle, Leslie A; Chiang, Kyle P; Yang, Xiang-Lei; Au, Kin-Fai; Wong, Wing Hung; Guo, Min; Zhang, Mingjie; Schimmel, Paul
Year of Publication: 2014
Journal: Science
Volume: 345
Issue: 6194
Pagination: 328-32
Date Published: 2014 Jul 18
Publication Language: eng
ISSN: 1095-9203
Keywords: Alternative Splicing, Amino Acyl-tRNA Synthetases, Catalysis, Catalytic Domain, Humans, Isoenzymes, Organ Specificity, Protein Isoforms, Recombinant Proteins

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.

DOI: 10.1126/science.1252943
Alternate Journal: Science