Non-POU domain-containing octamer-binding protein

NONO (Non-POU domain-containing octamer-binding protein) is a DNA- and RNA-binding protein involved in multiple nuclear processes, including pre-mRNA splicing, paraspeckle formation, and transcriptional regulation (UniProt: Q15233). It functions as a heterodimer with SFPQ and participates in DNA repair, circadian clock regulation, and viral immune responses through the cGAS-STING pathway. The protein also plays critical roles in synaptic organization by regulating GABAergic scaffold structure and neuronal differentiation through TET1 recruitment.

NONO is expressed broadly and has documented roles in neuronal function, particularly in regulating synaptic RNAs and gephyrin scaffold structure. A genetic association with X-linked intellectual developmental disorder (MRXS34) is noted in UniProt, reflecting its importance for neurodevelopment and cognitive function.

In Alzheimer's Disease, NONO is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change is 0.5869 across analyzed subcellular fractions, indicating a modest but consistent elevation. This upregulation may reflect altered RNA metabolism or compensatory nuclear processes in AD pathology.