Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation

Nascent polypeptide within the exit tunnel stabilizes the ribosome to counteract risky translation
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DOI:
10.15252/embj.2021108299
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发表时间:
2021-10-20
期刊:
影响因子:
11.4
通讯作者:
Taguchi, Hideki
Taguchi, Hideki
中科院分区:
生物学1区
文献类型:
--
作者:
Chadani, Yuhei;Sugata, Nobuyuki;Taguchi, Hideki

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不论氨基酸序列如何,持续的翻译延伸是生物体产生蛋白质组的先决条件。然而,新生多肽产品承担延伸流产的固有风险。例如,带有间断性脯氨酸的带负电荷序列,称为内在核糖体不稳定(IRD)序列,削弱了翻译核糖体复合物,导致某些新生链序列过早终止翻译。在这里,我们表明,由于新生多肽的两个特征,大多数位于开放阅读框中间的潜在IRD序列仍然是隐式的,不会中断翻译。首先,新生多肽本身跨越出口隧道,其次,其庞大的氨基酸残基占据隧道入口区域,从而起到桥梁作用,保护大小核糖体亚基不被解离。因此,新生多肽产品具有内在的能力,以确保延伸的连续性。
Continuous translation elongation, irrespective of amino acid sequences, is a prerequisite for living organisms to produce their proteomes. However, nascent polypeptide products bear an inherent risk of elongation abortion. For example, negatively charged sequences with occasional intermittent prolines, termed intrinsic ribosome destabilization (IRD) sequences, weaken the translating ribosomal complex, causing certain nascent chain sequences to prematurely terminate translation. Here, we show that most potential IRD sequences in the middle of open reading frames remain cryptic and do not interrupt translation, due to two features of the nascent polypeptide. Firstly, the nascent polypeptide itself spans the exit tunnel, and secondly, its bulky amino acid residues occupy the tunnel entrance region, thereby serving as a bridge and protecting the large and small ribosomal subunits from dissociation. Thus, nascent polypeptide products have an inbuilt ability to ensure elongation continuity.