Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Nucleic Acids Res. 2024 Nov 11;52(20):12582-12591. doi: 10.1093/nar/gkae870.
Poly(UG) or 'pUG' dinucleotide repeats are highly abundant sequences in eukaryotic RNAs. In Caenorhabditis elegans, pUGs are added to RNA 3' ends to direct gene silencing within Mutator foci, a germ granule condensate. Here, we show that pUG RNAs efficiently self-assemble into gel condensates through quadruplex (G4) interactions. Short pUG sequences form right-handed intermolecular G4s (pUG G4s), while longer pUGs form left-handed intramolecular G4s (pUG folds). We determined a 1.05 Å crystal structure of an intermolecular pUG G4, which reveals an eight stranded G4 dimer involving 48 nucleotides, 7 different G and U quartet conformations, 7 coordinated potassium ions, 8 sodium ions and a buried water molecule. A comparison of the intermolecular pUG G4 and intramolecular pUG fold structures provides insights into the molecular basis for G4 handedness and illustrates how a simple dinucleotide repeat sequence can form complex structures with diverse topologies.
多聚（UG）或“pUG”二核苷酸重复序列是真核 RNA 中高度丰富的序列。在秀丽隐杆线虫中，pUG 被添加到 RNA 3' 末端，以指导 Mutator 焦点（一种生殖颗粒凝聚物）内的基因沉默。在这里，我们表明 pUG RNA 通过四联体（G4）相互作用有效地自我组装成凝胶凝聚物。短的 pUG 序列形成右手分子间 G4（pUG G4），而较长的 pUG 形成左手分子内 G4（pUG 折叠）。我们确定了一个分子间 pUG G4 的 1.05 Å 晶体结构，揭示了一个涉及 48 个核苷酸、7 种不同的 G 和 U 四联体构象、7 个配位的钾离子、8 个钠离子和一个埋藏水分子的八链 G4 二聚体。分子间 pUG G4 和分子内 pUG 折叠结构的比较提供了对 G4 手性的分子基础的深入了解，并说明了简单的二核苷酸重复序列如何形成具有不同拓扑结构的复杂结构。
