p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: Implications for its physiological significance

doi:10.1073/pnas.122110199

p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: Implications for its physiological significance

National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-746, Korea

Edited by Paul R. Schimmel, The Scripps Research Institute, La Jolla, CA, and approved April 23, 2002 (received for review February 24, 2002)

Abstract

Mammalian tRNA synthetases form a macromolecular complex with three nonenzyme factors: p43, p38, and p18. Here we introduced a mutation within the mouse p38 gene to understand its functional significance for the formation of the multi-tRNA synthetase complex. The complex was completely disintegrated by the deficiency of p38. In addition, the protein levels and catalytic activities of the component enzymes and cofactors were severely decreased. A partial truncation of the p38 polypeptide separated the associated components into different subdomains. The mutant mice showed lethality within 2 days of birth. Thus, this work provides the first evidence, to our knowledge, that p38 is essential for the structural integrity of the multi-tRNA synthetase complex and mouse viability.

aminoacyl-tRNA synthetase‖macromolecular protein complex‖gene trap‖protein–protein interaction

Footnotes

↵ * Present address: Department of Molecular Biology, Dankook University, Seoul 140-714, Korea.
↵ † Present address: Graduate School of Biotechnology, Korea University, Seoul 136-701, Korea.
↵ ‡ To whom reprint requests should be addressed at: San 56–1, Shillim-dong, Kwanak-gu, Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-746, Korea. E-mail: sungkim{at}snu.ac.kr.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

ARSs,

aminoacyl-tRNA synthetases;

XRS,

the aminoacyl-tRNA synthetase of the substrate amino acid X;

MEF,

mouse embryonic fibroblast;

RT-PCR,

reverse transcription–PCR;

GAPDH,

glyceraldehyde 3 phosphate dehydrogenase