RNA homodimerization is important for various physiological processes, including the assembly of membraneless organelles, RNA subcellular localization, and packaging of viral genomes. However, understanding RNA dimerization has been hampered by the lack of systematic in vivo detection methods. Here, we show that CLASH, PARIS, and other RNA proximity ligation methods detect RNA homodimers transcriptome-wide as “overlapping” chimeric reads that contain more than one copy of the same sequence. Analyzing published proximity ligation data sets, we show that RNA:RNA homodimers mediated by direct base-pairing are rare across the human transcriptome, but highly enriched in specific transcripts, including U8 snoRNA, U2 snRNA, and a subset of tRNAs. Mutations in the homodimerization domain of U8 snoRNA impede dimerization in vitro and disrupt zebrafish development in vivo, suggesting an evolutionarily conserved role of this domain. Analysis of virus-infected cells reveals homodimerization of SARS-CoV-2 and Zika genomes, mediated by specific palindromic sequences located within protein-coding regions of N gene in SARS-CoV-2 and NS2A gene in Zika. We speculate that regions of viral genomes involved in homodimerization may constitute effective targets for antiviral therapies.

中文翻译：

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活细胞中 RNA 同源二聚体的全局定位

RNA 同二聚化对于各种生理过程都很重要，包括无膜细胞器的组装、RNA 亚细胞定位和病毒基因组的包装。然而，由于缺乏系统的体内检测方法，对 RNA 二聚化的理解受到了阻碍。在这里，我们展示了 CLASH、PARIS 和其他 RNA 邻近连接方法将 RNA 同源二聚体转录组范围检测为“重叠”嵌合读数，其中包含相同序列的多个拷贝。通过分析已发表的邻近连接数据集，我们发现由直接碱基配对介导的 RNA:RNA 同型二聚体在人类转录组中很少见，但在特定转录本中高度丰富，包括 U8 snoRNA、U2 snRNA 和tRNA子集。同二聚化域中的突变U8 snoRNA 在体外阻碍二聚化并在体内破坏斑马鱼的发育，表明该结构域具有进化上的保守作用。对病毒感染细胞的分析揭示了 SARS-CoV-2 和寨卡病毒基因组的同源二聚化，这是由位于 SARS-CoV-2 的N基因和寨卡病毒的NS2A基因的蛋白质编码区内的特定回文序列介导的。我们推测参与同二聚化的病毒基因组区域可能构成抗病毒治疗的有效靶点。