Mechanistic dissection of premature translation termination induced by acidic residues-enriched nascent peptide
Yuhei Chadani,
Takashi Kanamori,
Tatsuya Niwa,
Kazuya Ichihara,
Keiichi I. Nakayama,
Akinobu Matsumoto,
Hideki Taguchi
Affiliations
Yuhei Chadani
Faculty of Environmental, Life, Natural Science and Technology, Okayama University, Okayama 700-8530, Japan; Corresponding author
Takashi Kanamori
GeneFrontier Corporation, Kashiwa-shi, Chiba 277-0005, Japan
Tatsuya Niwa
Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan
Kazuya Ichihara
Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
Keiichi I. Nakayama
Anticancer Strategies Laboratory, TMDU Advanced Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan; Division of Cell Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan
Akinobu Matsumoto
Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan
Hideki Taguchi
Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan; School of Life Science and Technology, Tokyo Institute of Technology, Yokohama 226-8503, Japan; Corresponding author
Summary: Ribosomes polymerize nascent peptides through repeated inter-subunit rearrangements between the classic and hybrid states. The peptidyl-tRNA, the intermediate species during translation elongation, stabilizes the translating ribosome to ensure robust continuity of elongation. However, the translation of acidic residue-rich sequences destabilizes the ribosome, leading to a stochastic premature translation cessation termed intrinsic ribosome destabilization (IRD), which is still ill-defined. Here, we dissect the molecular mechanisms underlying IRD in Escherichia coli. Reconstitution of the IRD event reveals that (1) the prolonged ribosome stalling enhances IRD-mediated translation discontinuation, (2) IRD depends on temperature, (3) the destabilized 70S ribosome complex is not necessarily split, and (4) the destabilized ribosome is subjected to peptidyl-tRNA hydrolase-mediated hydrolysis of the peptidyl-tRNA without subunit splitting or recycling factors-mediated subunit splitting. Collectively, our data indicate that the translation of acidic-rich sequences alters the conformation of the 70S ribosome to an aberrant state that allows the noncanonical premature termination.
