Cell Biology Center, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Japan.
School of Life Science and Technology, Tokyo Institute of Technology, Yokohama, Japan.
EMBO J. 2021 Dec 1;40(23):e108299. doi: 10.15252/embj.2021108299. Epub 2021 Oct 20.
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.
连续的翻译延伸，无论氨基酸序列如何，都是生物体产生其蛋白质组的前提。然而，新生多肽产物带有延伸中止的固有风险。例如，带有偶尔间歇性脯氨酸的带负电荷的序列，称为内在核糖体失稳 (IRD) 序列，削弱了正在翻译的核糖体复合物，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，开放阅读框中间的大多数潜在的 IRD 序列仍然是隐藏的，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，从而充当桥梁并保护大亚基和小亚基不分离。因此，新生多肽产物具有内在的确保延伸连续性的能力。
