NONO

Description

The NONO (non-POU domain containing octamer binding) is a protein-coding gene located on chromosome X.

Non-POU domain-containing octamer-binding protein (NonO) is a protein that in humans is encoded by the NONO gene. The NonO protein belongs to the Drosophila behaviour/human splicing (DBHS) family of proteins. Proteins in the DHBS family include mammalian SFPQ (splicing factor, proline- and glutamine-rich; a.k.a. PSF), NONO (Non-POU domain-containing octamer-binding protein; a.k.a. p54nrb) and PSPC1 (paraspeckle component 1; a.k.a. PSP1) and invertebrate NONA (Protein no-on-transient A) and Hrp65. NONO has been shown to interact with SFPQ, SPI1 and Androgen receptor. NONO is involved with many nuclear processes and binds to both DNA and RNA. The NONO protein has been shown to be implicated in many biological functions including, pre-mRNA splicing; activation of transcription; termination of transcription; DNA unwinding and pairing and maintaining correct circadian clock function. NONO has been identified to bind with Rasd1 protein, resulting dimer Rasd1 may act to modulate the function of NONO to down regulate the expression of the CREB genes, NR4A1 and Nr4A2.

NONO, also known as p54nrb, is a DNA- and RNA-binding protein involved in various nuclear processes. It binds to the octamer sequence in double-stranded DNA and to single-stranded DNA and RNA at a distinct site. NONO participates in pre-mRNA splicing, likely as a heterodimer with SFPQ, and interacts with U5 snRNA. Together with PSPC1, it is crucial for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer, in association with MATR3, might play a role in retaining defective RNAs within the nucleus. This heteromer might also be involved in DNA unwinding by modulating the function of topoisomerase I (TOP1) and in DNA non-homologous end joining (NHEJ) for double-strand break repair and V(D)J recombination, potentially stabilizing paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, directly binds to DNA substrates, and collaborates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to form a functional preligation complex. NONO contributes to transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. NONO also binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Additionally, it regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. NONO is essential for the functional organization of GABAergic synapses, specifically regulating synaptic RNAs and the GPHN/gephyrin scaffold structure through the regulation of the GABRA2 transcript. During neuronal differentiation, NONO plays a crucial role by recruiting TET1 to genomic loci, thereby regulating 5-hydroxymethylcytosine levels. NONO participates in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex. This complex serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway. NONO promotes activation of the cGAS-STING pathway in response to HIV-2 infection by interacting with the HIV-2 Capsid protein p24, enhancing the detection of viral DNA by CGAS and leading to CGAS-mediated immune activation. However, its weak interaction with HIV-1 Capsid protein p24 does not trigger activation of the cGAS-STING pathway. NONO exists as a monomer and as part of the SFPQ-NONO complex, likely a heterotetramer composed of two 52 kDa (NONO) and two 100 kDa (SFPQ) subunits. It is a component of the spliceosome and U5.4/6 snRNP complexes. NONO interacts with CPNE4 (via the VWFA domain), forms heterodimers with PSPC1 through the formation of a coiled coil domain, and is part of a complex containing SFPQ, NONO, and MATR3. Additionally, it is part of complexes with SFPQ, NONO, and NR5A1; SFPQ, NONO, and TOP1; and interacts with SPI1 and SPIB. NONO interacts with RNF43, PER1, and PER2, and is part of the HDP-RNP complex consisting of HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3), and NEAT1 RNA. It interacts with WASL (via the second RRM domain) directly, forming a multiprotein complex with WASL and SFPQ. NONO also interacts with ERCC6 and TET1 (via the DNA-binding domain). In the context of microbial infection, NONO interacts with HIV-2 Capsid protein p24 with high affinity and with HIV-1 Capsid protein p24 with low affinity.

NONO is also known as MRXS34, NMT55, NRB54, P54, P54NRB, PPP1R114.

Associated Diseases

WES Whole Exome Sequencing