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.
摘要：
核糖体通过经典状态和杂合状态之间重复的亚基间重排来聚合新生肽。肽基-tRNA,翻译延伸过程中的中间物种，稳定翻译核糖体，以确保延伸的强大连续性。然而,富含酸性残基的序列的翻译使核糖体不稳定，导致随机的过早翻译停止，称为内在核糖体不稳定（IRD），这仍然是不明确的。这里,我们剖析了大肠杆菌IRD的分子机制。IRD事件的重建揭示了（1）延长的核糖体停滞增强IRD介导的翻译中断，(2)IRD取决于温度，(3)不稳定的70S核糖体复合物不一定分裂，和(4)使去稳定的核糖体经受肽基-tRNA水解酶介导的肽基-tRNA水解而没有亚基分裂或再循环因子介导的亚基分裂。总的来说，我们的数据表明,富含酸性序列的翻译将70S核糖体的构象改变为允许非规范过早终止的异常状态.
