Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Trends Biochem Sci. 2023 Aug;48(8):689-698. doi: 10.1016/j.tibs.2023.04.003. Epub 2023 May 6.
Biomolecular condensates (BMCs) can facilitate or inhibit diverse cellular functions. BMC formation is driven by noncovalent protein-protein, protein-RNA, and RNA-RNA interactions. Here, we focus on Tudor domain-containing proteins - such as survival motor neuron protein (SMN) - that contribute to BMC formation by binding to dimethylarginine (DMA) modifications on protein ligands. SMN is present in RNA-rich BMCs, and its absence causes spinal muscular atrophy (SMA). SMN's Tudor domain forms cytoplasmic and nuclear BMCs, but its DMA ligands are largely unknown, highlighting open questions about the function of SMN. Moreover, DMA modification can alter intramolecular interactions and affect protein localization. Despite these emerging functions, the lack of direct methods of DMA detection remains an obstacle to understanding Tudor-DMA interactions in cells.
生物分子凝聚物 (BMCs) 可以促进或抑制多种细胞功能。BMC 的形成是由非共价的蛋白质-蛋白质、蛋白质-RNA 和 RNA-RNA 相互作用驱动的。在这里,我们专注于含有 Tudor 结构域的蛋白质,如运动神经元生存蛋白 (SMN),它通过与蛋白质配体上的二甲基精氨酸 (DMA) 修饰结合,有助于 BMC 的形成。SMN 存在于富含 RNA 的 BMC 中,其缺失会导致脊髓性肌萎缩症 (SMA)。SMN 的 Tudor 结构域形成细胞质和核 BMC,但它的 DMA 配体在很大程度上是未知的,这凸显了关于 SMN 功能的开放性问题。此外,DMA 修饰可以改变分子内相互作用并影响蛋白质定位。尽管有这些新出现的功能,但缺乏直接检测 DMA 的方法仍然是理解细胞中 Tudor-DMA 相互作用的障碍。