Abnormal SAFB1 expression and localisation are hallmarks of spinocerebellar ataxias and Huntington’s chorea: increased and ectopic expression of the RNA binding protein SAFB1 in the neurons of spinocerebellar ataxia and Huntington’s chorea patients

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SAFB1 is a DNA and RNA binding protein that is highly expressed in the cerebellum and hippocampus and is involved in the processing of coding and non-coding RNAs, splicing and dendritic function. We analysed SAFB1 expression in the post-mortem brain tissue of spinocerebellar ataxia (SCA), Huntington’s disease (HD), Multiple sclerosis (MS), Parkinson’s disease patients and controls. In SCA cases expression of SAFB1 in the nucleus was increased and there was abnormal and extensive expression in the cytoplasm where it co-localised with markers of Purkinje cell injury. Significantly, no SAFB1 expression was found in the cerebellar neurons of the dentate nucleus in control or MS patients, however in SCA patients SAFB1 expression was increased significantly in both the nucleus and cytoplasm of dentate neurons. In HD, we found SAFB1 expression was increased in the nucleus and cytoplasm of striatal neurons, however there was no SAFB1 staining in the striatal neurons of controls. In PD substantia nigra we did not see any changes in neuronal SAFB1 expression. iCLIP analysis found SAFB1 crosslink sites within ATXN1 RNA were adjacent to the start and within the glutamine repeat sequence. Further investigation found increased binding of SAFB1 to pathogenic ATXN1-85Q mRNA. These novel data strongly suggest SAFB1 contributes to the aetiology of SCA and Huntington’s chorea and that it may be a pathological marker of polyglutamine repeat expansion diseases.
Original languageEnglish
JournalBrain Pathology
Publication statusAccepted/In press - 2 Jun 2020



  • Huntington's chorea
  • spinocerebellar ataxia
  • Parkinson's disease
  • polyglutamine
  • SAFB1
  • RNA binding protein (RBP)

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