School of Dentistry and Medical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia.
Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC 3010, Australia.
Cells. 2024 Jul 16;13(14):1202. doi: 10.3390/cells13141202.
SOX proteins are a family of transcription factors (TFs) that play critical functions in sex determination, neurogenesis, and chondrocyte differentiation, as well as cardiac, vascular, and lymphatic development. There are 20 SOX family members in humans, each sharing a 79-residue L-shaped high mobility group (HMG)-box domain that is responsible for DNA binding. SOX2 was recently shown to interact with long non-coding RNA and large-intergenic non-coding RNA to regulate embryonic stem cell and neuronal differentiation. The RNA binding region was shown to reside within the HMG-box domain; however, the structural details of this binding remain unclear. Here, we show that all SOX family members, except group H, interact with RNA. Our mutational experiments demonstrate that the disordered C-terminal region of the HMG-box domain plays an important role in RNA binding. Further, by determining a high-resolution structure of the HMG-box domain of the group H family member SOX30, we show that despite differences in RNA binding ability, SOX30 shares a very similar secondary structure with other SOX protein HMG-box domains. Together, our study provides insight into the interaction of SOX TFs with RNA.
SOX 蛋白是一类转录因子（TFs），在性别决定、神经发生和软骨细胞分化以及心脏、血管和淋巴管发育中发挥关键作用。人类有 20 种 SOX 家族成员，每个成员都共享一个负责 DNA 结合的 79 残基的 L 形高迁移率族（HMG）-盒结构域。最近的研究表明，SOX2 与长链非编码 RNA 和大基因间非编码 RNA 相互作用，以调节胚胎干细胞和神经元分化。RNA 结合区域被证明位于 HMG 盒结构域内；然而，这种结合的结构细节尚不清楚。在这里，我们表明除了 H 组之外，所有 SOX 家族成员都与 RNA 相互作用。我们的突变实验表明，HMG 盒结构域的无规卷曲 C 端区域在 RNA 结合中起着重要作用。此外，通过确定 H 组家族成员 SOX30 的 HMG 盒结构域的高分辨率结构，我们表明尽管 RNA 结合能力存在差异，但 SOX30 与其他 SOX 蛋白 HMG 盒结构域具有非常相似的二级结构。总之，我们的研究提供了对 SOX TFs 与 RNA 相互作用的深入了解。
