The ubiquitin hybrid gene UBA52 regulates ubiquitination of ribosome and sustains embryonic development.
Ubiquitination is a crucial post-translational modification; however, the functions of ubiquitin-coding genes remain unclear. UBA52 encodes a fusion protein comprising ubiquitin at the N-terminus and ribosomal protein L40 (RPL40) at the C-terminus. Here we showed that Uba52-deficient mice die during embryogenesis. UBA52-deficient cells exhibited normal levels of total ubiquitin. However, UBA52-deficient cells displayed decreased protein synthesis and cell-cycle arrest. The overexpression of UBA52 ameliorated the cell-cycle arrest caused by UBA52 deficiency. Surprisingly, RPL40 expression itself is insufficient to regulate cyclin D expression. The cleavage of RPL40 from UBA52 was required for maintaining protein synthesis. Furthermore, we found that RPL40 formed a ribosomal complex with ubiquitin cleaved from UBA52. UBA52 supplies RPL40 and ubiquitin simultaneously to the ribosome. Our study demonstrated that the ubiquitin-coding gene UBA52 is not just an ubiquitin supplier to the ubiquitin pool but is also a regulator of the ribosomal protein complex. These findings provide novel insights into the regulation of ubiquitin-dependent translation and embryonic development.
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Masanori
M
Kobayashi
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Shigeru
S
Oshima
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Chiaki
C
Maeyashiki
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Yoichi
Y
Nibe
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Kana
K
Otsubo
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Yu
Y
Matsuzawa
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Yasuhiro
Y
Nemoto
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Takashi
T
Nagaishi
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.|Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Ryuichi
R
Okamoto
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Kiichiro
K
Tsuchiya
Department of Advanced Therapeutics for GI Diseases, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Tetsuya
T
Nakamura
Department of Gastroenterology and Hepatology, Graduate School, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Mamoru
M
Watanabe
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D047108:Embryonic Development; D005804:Genes, Lethal; D006801:Humans; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D054875:Ubiquitination
D012269:Ribosomal Proteins; C000627486:UBA52 protein, human; D025801:Ubiquitin