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PolyG Fibrils Coalesce Into Nuclear Ribbons That Engage Proteostasis Machinery in Neuronal Intranuclear Inclusion
Hui Dong1, Yongcheng Pan2, Zhiyao Tang3
1Interdisciplinary Research Center on Biology and Chemistry, State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 20, 2026
Summary
Neuronal intranuclear inclusion disease (NIID) is caused by GGC repeat expansions. Researchers discovered that the resulting polyglycine (polyG) proteins form ribbon-like structures in neuronal nuclei, impacting disease mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Neuronal intranuclear inclusion disease (NIID) is characterized by polyglycine (polyG) protein accumulation in neuronal nuclei.
- The precise ultrastructure and pathological role of these polyG aggregates are not well understood.
Purpose of the Study:
- To elucidate the native cellular ultrastructure of polyG assemblies in NIID.
- To investigate the interaction of polyG aggregates with cellular proteostasis machinery.
Main Methods:
- Cryo-electron tomography (cryo-ET) was used to characterize polyG architecture in vitro and in situ.
- Proximity-dependent labeling coupled with mass spectrometry identified interacting proteins.
Main Results:
- Polyglycine forms branched fibrils that coalesce into ribbon-shaped structures within neuronal nuclei.
- Proteasome subunits and molecular chaperones were found to be selectively enriched at polyG assemblies.
- Cryo-ET visualized proteasome-like particles associated with polyG ribbons.
Conclusions:
- Polyglycine in NIID forms unexpected ribbon-shaped supramolecular assemblies.
- These nuclear polyG ribbons may act as scaffolds that engage the cell's proteostasis machinery, offering mechanistic insights into NIID pathogenesis.
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