Regulation of BRCA1 stability through the tandem UBX domains of isoleucyl-tRNA synthetase 1

Scisung Chung, Mi Sun Kang, Dauren S. Alimbetov, Gil Im Mun, Na Oh Yunn, Yunjin Kim, Byung Gyu Kim, Minwoo Wie, Eun A. Lee, Jae Sun Ra, Jung Min Oh, Donghyun Lee, Keondo Lee, Jihan Kim, Seung Hyun Han, Kyong Tai Kim, Wan Kyun Chung, Ki Hyun Nam, Jaehyun Park, Byung Hoon LeeSunghoon Kim, Weixing Zhao, Sung Ho Ryu, Yun Sil Lee, Kyungjae Myung, Yunje Cho

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Aminoacyl-tRNA synthetases (ARSs) have evolved to acquire various additional domains. These domains allow ARSs to communicate with other cellular proteins in order to promote non-translational functions. Vertebrate cytoplasmic isoleucyl-tRNA synthetases (IARS1s) have an uncharacterized unique domain, UNE-I. Here, we present the crystal structure of the chicken IARS1 UNE-I complexed with glutamyl-tRNA synthetase 1 (EARS1). UNE-I consists of tandem ubiquitin regulatory X (UBX) domains that interact with a distinct hairpin loop on EARS1 and protect its neighboring proteins in the multi-synthetase complex from degradation. Phosphomimetic mutation of the two serine residues in the hairpin loop releases IARS1 from the complex. IARS1 interacts with BRCA1 in the nucleus, regulates its stability by inhibiting ubiquitylation via the UBX domains, and controls DNA repair function.

Original languageEnglish (US)
Article number6732
JournalNature communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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