MOE Key Laboratory for Cellular Dynamics, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, 230027, Hefei, China.
Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Nicolás Cabrera 1, 28049, Madrid, Spain.
Nat Commun. 2022 Sep 2;13(1):5166. doi: 10.1038/s41467-022-32883-z.
Gemin5 in the Survival Motor Neuron (SMN) complex serves as the RNA-binding protein to deliver small nuclear RNAs (snRNAs) to the small nuclear ribonucleoprotein Sm complex via its N-terminal WD40 domain. Additionally, the C-terminal region plays an important role in regulating RNA translation by directly binding to viral RNAs and cellular mRNAs. Here, we present the three-dimensional structure of the Gemin5 C-terminal region, which adopts a homodecamer architecture comprised of a dimer of pentamers. By structural analysis, mutagenesis, and RNA-binding assays, we find that the intact pentamer/decamer is critical for the Gemin5 C-terminal region to bind cognate RNA ligands and to regulate mRNA translation. The Gemin5 high-order architecture is assembled via pentamerization, allowing binding to RNA ligands in a coordinated manner. We propose a model depicting the regulatory role of Gemin5 in selective RNA binding and translation. Therefore, our work provides insights into the SMN complex-independent function of Gemin5.
Gemin5 在运动神经元存活（SMN）复合物中作为 RNA 结合蛋白，通过其 N 端 WD40 结构域将小核 RNA（snRNA）递送到小核核糖核蛋白 Sm 复合物。此外，C 端区域通过直接与病毒 RNA 和细胞 mRNA 结合，在调节 RNA 翻译方面发挥重要作用。在这里，我们呈现了 Gemin5 C 端区域的三维结构，该结构采用由五聚体二聚体组成的同源十聚体架构。通过结构分析、突变和 RNA 结合测定，我们发现完整的五聚体/十聚体对于 Gemin5 C 端区域结合同源 RNA 配体和调节 mRNA 翻译至关重要。Gemin5 的高级结构通过五聚化组装，允许以协调的方式结合 RNA 配体。我们提出了一个模型，描绘了 Gemin5 在选择性 RNA 结合和翻译中的调节作用。因此，我们的工作为 Gemin5 在 SMN 复合物非依赖性功能提供了深入了解。
