G-quadruplex structures trigger RNA phase separation

Yueying Zhang, Minglei Yang, Susan Duncan, Xiaofei Yang, Mahmoud Abdelhamid, Lin Huang, Huakun Zhang, Philip N Benfey, Zoe Waller, Yiliang Ding

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Liquid–liquid phase separation plays an important role in a variety of cellular processes, including the formation of membrane-less organelles, the cytoskeleton, signalling complexes, and many other biological supramolecular assemblies. Studies on the molecular basis of phase separation in cells have focused on protein-driven phase separation. In contrast, there is limited understanding on how RNA specifically contributes to phase separation. Here, we described a phase-separation-like phenomenon that SHORT ROOT (SHR) RNA undergoes in cells. We found that an RNA G-quadruplex (GQ) forms in SHR mRNA and is capable of triggering RNA phase separation under physiological conditions, suggesting that GQs might be responsible for the formation of the SHR phase-separation-like phenomenon in vivo. We also found the extent of GQ-triggered-phase-separation increases on exposure to conditions which promote GQ. Furthermore, GQs with more G-quartets and longer loops are more likely to form phase separation. Our studies provide the first evidence that RNA can adopt structural motifs to trigger and/or maintain the specificity of RNA-driven phase separation.
Original languageEnglish
Pages (from-to)11746–11754
JournalNucleic Acids Research
Issue number22
Early online date13 Nov 2019
Publication statusPublished - 16 Dec 2019

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