{Reference Type}: Journal Article
{Title}: Mechanistic dissection of premature translation termination induced by acidic residues-enriched nascent peptide.
{Author}: Chadani Y;Kanamori T;Niwa T;Ichihara K;Nakayama KI;Matsumoto A;Taguchi H;
{Journal}: Cell Rep
{Volume}: 42
{Issue}: 12
{Year}: 2023 12 26
暂无{DOI}: 10.1016/j.celrep.2023.113569
{Abstract}: 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.