Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University, New York, NY 10065, USA.
Tri-Institutional Training Program in Chemical Biology, The Rockefeller University, New York, NY 10065, USA.
Science. 2021 Sep 10;373(6560):eabj5338. doi: 10.1126/science.abj5338.
The human small subunit processome mediates early maturation of the small ribosomal subunit by coupling RNA folding to subsequent RNA cleavage and processing steps. We report the high-resolution cryo–electron microscopy structures of maturing human small subunit (SSU) processomes at resolutions of 2.7 to 3.9 angstroms. These structures reveal the molecular mechanisms that enable crucial progressions during SSU processome maturation. RNA folding states within these particles are communicated to and coordinated with key enzymes that drive irreversible steps such as targeted exosome-mediated RNA degradation, protein-guided site-specific endonucleolytic RNA cleavage, and tightly controlled RNA unwinding. These conserved mechanisms highlight the SSU processome’s impressive structural plasticity, which endows this 4.5-megadalton nucleolar assembly with the distinctive ability to mature the small ribosomal subunit from within.
人类小亚基加工体通过将 RNA 折叠与随后的 RNA 切割和加工步骤偶联，介导小核糖体亚基的早期成熟。我们报道了分辨率为 2.7 至 3.9 埃的成熟人类小亚基（SSU）加工体的高分辨率冷冻电镜结构。这些结构揭示了在 SSU 加工体成熟过程中能够实现关键进展的分子机制。这些颗粒内的 RNA 折叠状态与驱动不可逆步骤的关键酶进行通讯和协调，这些步骤包括靶向 exosome 介导的 RNA 降解、蛋白引导的位点特异性内切核酸酶切割以及严格控制的 RNA 解旋。这些保守的机制突出了 SSU 加工体令人印象深刻的结构可塑性，这使这个 450 万道尔顿的核仁组装体具有从内部成熟小核糖体亚基的独特能力。
