AIMP3 depletion causes genome instability and loss of stemness in mouse embryonic stem cells

• Published in: Cell death & disease Vol. 9; no. 10; pp. 972 - 14
• Main Authors: Kim, Sun Mi, Jeon, Yoon, Kim, Doyeun, Jang, Hyonchol, Bae, June Sung, Park, Mi Kyung, Kim, Hongtae, Kim, Sunghoon, Lee, Ho
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2018; Springer Nature B.V
• Subjects: 13/100; 13/109; 13/95; 38/61; 42/41; 42/89; 64/60; 82/80; 96/1; 96/31; 96/34; 96/63; Aminoacyl-tRNA ligase; Antibodies; Biochemistry; Biomedical and Life Sciences; Blastocysts; Cell Biology; Cell Culture; Cell self-renewal; DNA damage; DNA microarrays; Double-strand break repair; Embryo cells; Embryogenesis; Embryos; Genomes; Genomic instability; Homologous recombination; Immunology; Lethality; Life Sciences; p53 Protein; Signal transduction; Stem cell transplantation; Stem cells; tRNA
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-018-1037-4

Aminoacyl-tRNA synthetase-interacting multifunctional protein-3 (AIMP3) is a component of the multi-aminoacyl-tRNA synthetase complex and is involved in diverse cellular processes. Given that AIMP3 deficiency causes early embryonic lethality in mice, AIMP3 is expected to play a critical role in early mouse development. To elucidate a functional role of AIMP3 in early mouse development, we induced AIMP3 depletion in mouse embryonic stem cells (mESCs) derived from blastocysts of AIMP3 f/f ; Cre ERT2 mice. In the present study, AIMP3 depletion resulted in loss of self-renewal and ability to differentiate to three germ layers in mESCs. AIMP3 depletion led to accumulation of DNA damage by blocking double-strand break repair, in particular homologous recombination. Through microarray analysis, the p53 signaling pathway was identified as being activated in AIMP3-depleted mESCs. Knockdown of p53 rescued loss of stem cell characteristics by AIMP3 depletion in mESCs. These results imply that AIMP3 depletion in mESCs leads to accumulation of DNA damage and p53 transactivation, resulting in loss of stemness. We propose that AIMP3 is involved in maintenance of genome stability and stemness in mESCs.