Publication Date:
2014-07-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188629/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4188629/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- R01 CA092577/CA/NCI NIH HHS/ -- R01 GM088278/GM/NIGMS NIH HHS/ -- R01 GM100136/GM/NIGMS NIH HHS/ -- R01 HG005717/HG/NHGRI NIH HHS/ -- R01 NS085092/NS/NINDS NIH HHS/ -- R01CA92577/CA/NCI NIH HHS/ -- R01GM088278/GM/NIGMS NIH HHS/ -- R01GM100136/GM/NIGMS NIH HHS/ -- R01HG005717/HG/NHGRI NIH HHS/ -- R01NS085092/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2014 Jul 18;345(6194):328-32. doi: 10.1126/science.1252943.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IAS HKUST-Scripps R&D Laboratory, Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Pangu Biopharma, Edinburgh Tower, The Landmark, 15 Queen's Road Central, Hong Kong, China. ; The Scripps Laboratories for tRNA Synthetase Research, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA. aTyr Pharma, 3545 John Hopkins Court, Suite 250, San Diego, CA 92121, USA. ; aTyr Pharma, 3545 John Hopkins Court, Suite 250, San Diego, CA 92121, USA. ; IAS HKUST-Scripps R&D Laboratory, Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. The Scripps Laboratories for tRNA Synthetase Research, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA. ; Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. ; Department of Statistics, Stanford University, Stanford, CA 94305, USA. ; The Scripps Laboratories for tRNA Synthetase Research, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA. ; IAS HKUST-Scripps R&D Laboratory, Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. ; IAS HKUST-Scripps R&D Laboratory, Institute for Advanced Study, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. The Scripps Laboratories for tRNA Synthetase Research, The Scripps Research Institute, 10650 North Torrey Pines Road, La Jolla, CA 92037, USA. The Scripps Laboratories for tRNA Synthetase Research, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA. schimmel@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25035493" target="_blank"〉PubMed〈/a〉
Keywords:
Alternative Splicing
;
Amino Acyl-tRNA Synthetases/chemistry/genetics/*metabolism
;
Catalysis
;
*Catalytic Domain
;
Humans
;
Isoenzymes/chemistry/genetics/metabolism
;
Organ Specificity
;
Protein Isoforms/chemistry/genetics/metabolism
;
Recombinant Proteins/chemistry/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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