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Updated: Jun 12, 2025

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
RNF219 RING Finger Domain Mutants Drive Phase Separation to Encapsulate CCR4-NOT and Promote Cell Proliferation
Chen Chen1, Chenghao Guo1, Ke Fang1
1Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing, China.
Abstract:
RING finger protein 219 (RNF219) is a co-factor for the CCR4-NOT deadenylase complex in mammals. Here, we found that mutations within the C3HC4 scaffold of the RING finger domain in RNF219 are capable of forming condensates via liquid-liquid phase separation (LLPS), though the wild-type RING finger domain intrinsically suppresses LLPS. We further demonstrated that the adjacent coiled-coil 1 (CC1) domain promotes the potential of RNF219 to form condensates. Moreover, the mutant RNF219 condensates are able to encapsulate the CCR4-NOT complex, inhibiting the RNA deadenylation activity of CCR4-NOT. Additionally, we observed that RNF219 mutations could promote cell proliferation. These findings suggest a pathogenic mechanism whereby RNF219 mutations could induce CCR4-NOT condensate formation, inhibit deadenylation-dependent mRNA decay and drive cell proliferation.
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