Structural basis for Gemin5 decamer-mediated mRNA binding

• Published in: Nature communications Vol. 13; no. 1; p. 5166
• Main Authors: Guo, Qiong, Zhao, Shidong, Francisco-Velilla, Rosario, Zhang, Jiahai, Embarc-Buh, Azman, Abellan, Salvador, Lv, Mengqi, Tang, Peiping, Gong, Qingguo, Shen, Huaizong, Sun, Linfeng, Yao, Xuebiao, Min, Jinrong, Shi, Yunyu, Martínez-Salas, Encarnacion, Zhang, Kaiming, Xu, Chao
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 147/28; 631/45/500; 631/535/1258; 82/80; 82/83; Cellular structure; Humanities and Social Sciences; Ligands; mRNA; multidisciplinary; Mutagenesis; RNA-binding protein; Science; Science (multidisciplinary); Structural analysis; Translation
• ISSN: 2041-1723; 2041-1723
• 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. Structural biology, complemented by biochemistry experiments and RNA-binding assays show that the Gemin5 C-terminal region adopts a decamer architecture. Gemin5 decamerization is essential for its role in regulating mRNA translation.