Accumulation of FAM98B and tRNA-Splicing Ligase Complex Proteins in Neuronal Intranuclear Inclusions in Spinocerebellar ataxia type 4.

In pontine neurons from a genetically confirmed SCA4 patient, tRNA-splicing ligase complex proteins FAM98B, RTRAF, and RTCB accumulate in neuronal intranuclear inclusions, forming an outer layer around a ubiquitin inner layer.

• Why it matters: SCA4 involves p62- and ubiquitin-positive NIIs, and in other polyglycine disorders these inclusions sequester tRNA-LC proteins, producing downstream dysfunction tied to neurodegeneration.
• What they did: The study used postmortem brain tissue from one SCA4 patient, applying immunofluorescence confocal microscopy across multiple regions to localize p62, ubiquitin, and tRNA-LC proteins FAM98B, RTRAF, and RTCB.
• The result: Inclusion incorporation coincided with depletion of FAM98B, RTRAF, and RTCB from the soluble nucleoplasm, linking SCA4 to a shared tRNA-LC dysfunction phenotype seen in other GGC-repeat disorders.

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