NONO Protein, Human (His, Strep)

NONO is a DNA- and RNA-binding protein involved in various nuclear processes. It binds to the conventional octamer sequence in double-stranded DNA and independently interacts with single-stranded DNA and RNA. NONO likely participates in pre-mRNA splicing as a heterodimer with SFPQ and interacts with U5 snRNA. Together with PSPC1, it is essential for the formation of nuclear paraspeckles. The SFPQ-NONO heterodimer, associated with MATR3, may play a role in nuclear retention of defective RNAs and could modulate DNA unwinding by regulating topoisomerase I/TOP1. Additionally, this dimer is involved in DNA non-homologous end joining (NHEJ), contributing to double-strand break repair and V(D)J recombination. NONO also participates in transcriptional regulation, such as the SFPQ-NONO-NR5A1 complex binding to the CYP17 promoter to modulate transcriptional activity. By similarity, NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) to activate transcription, represses CLOCK-BMAL1 heterodimer activity to regulate the circadian clock, plays a critical role in GABAergic synapse organization, regulates synaptic RNAs and GPHN/gephyrin scaffold structure via GABRA2 transcript modulation, and recruits TET1 during neuronal differentiation to regulate 5-hydroxymethylcytosine levels. NONO also contributes to DNA virus-mediated innate immune responses by assembling into the HDP-RNP complex, which serves as a platform for IRF3 phosphorylation and activates the cGAS-STING pathway. During HIV-2 infection, NONO interacts with HIV-2 Capsid protein p24 to promote viral DNA detection by CGAS, triggering immune activation, whereas its weak interaction with HIV-1 Capsid protein p24 does not activate this pathway.