Non-POU domain-containing octamer-binding protein (NONO (also commonly known as p54nrb))

Non-POU domain-containing octamer-binding protein (NONO, also known as p54nrb) is a multifunctional nuclear protein and member of the Drosophila behaviour/human splicing (DBHS) family. It binds both DNA and RNA, mediating diverse nuclear functions including pre-mRNA splicing, transcriptional regulation, DNA unwinding, and participation in nonhomologous end joining (NHEJ) for DNA repair. NONO forms functional dimers, commonly with SFPQ or PSPC1, and contributes to the assembly of paraspeckles—nuclear substructures involved in the retention of defective RNAs. Aberrant expression of NONO is implicated in a range of human diseases, especially in oncogenesis where it promotes tumor growth, metastasis, and impacts key signaling pathways such as Akt/MAPK and β-catenin. While NONO is investigated as a cancer biomarker and potential therapeutic target, the lack of selective drugs and its critical roles in normal cell biology present substantial safety and specificity challenges for therapeutic modulation.

Other names

NMT55NRB54Nuclear RNA-binding protein, 54-kDP54P54NRBPPP1R114protein phosphatase 1 regulatory subunit 114non-Pou domain-containing octamer (ATGCAAAT) binding proteinp54nrbNONO_HUMAN

Experimental silencing (e.g., CRISPR/Cas9) of NONO leads to inhibition of tumorigenic properties in cancer cells, including cell growth, migration, invasion, and stemness (by modulating Akt/MAPK/β-catenin pathways); no currently approved small-molecule or biologic modulators