======= NONO =======
== Gene Information ==
* **Official Symbol**: NONO
* **Official Name**: non-POU domain containing octamer binding
* **Aliases and Previous Symbols**: N/A
* **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4841|4841]]
* **UniProt**: [[https://www.uniprot.org/uniprot/Q15233|Q15233]]
* **Interactions**: [[https://thebiogrid.org/search.php?search=NONO&organism=9606|BioGRID]]
* **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20NONO|Open PubMed]]
* **OMIM**: [[https://omim.org/entry/300084|Open OMIM]]
== Function Summary ==
* **Entrez Summary**: This gene encodes an RNA-binding protein which plays various roles in the nucleus, including transcriptional regulation and RNA splicing. A rearrangement between this gene and the transcription factor E3 gene has been observed in papillary renal cell carcinoma. Alternatively spliced transcript variants have been described. Pseudogenes exist on Chromosomes 2 and 16. [provided by RefSeq, Feb 2009].
* **UniProt Summary**: DNA- and RNA binding protein, involved in several nuclear processes. Binds the conventional octamer sequence in double-stranded DNA. Also binds single-stranded DNA and RNA at a site independent of the duplex site. Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ. Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b. Together with PSPC1, required for the formation of nuclear paraspeckles. The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs. The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1. The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends. In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex. NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP- dependent transcriptional activity. NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. Important for the functional organization of GABAergic synapses. Plays a specific and important role in the regulation of synaptic RNAs and GPHN/gephyrin scaffold structure, through the regulation of GABRA2 transcript. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS- STING pathway (PubMed:28712728). {ECO:0000250|UniProtKB:Q99K48, ECO:0000269|PubMed:10858305, ECO:0000269|PubMed:11525732, ECO:0000269|PubMed:11897684, ECO:0000269|PubMed:15590677, ECO:0000269|PubMed:22416126, ECO:0000269|PubMed:26571461, ECO:0000269|PubMed:28712728}.
|NOPS|
|RRM 1|
|negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway|
|paraspeckles|
|regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway|
|negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway|
|negative regulation of oxidative stress-induced neuron death|
|regulation of oxidative stress-induced neuron death|
|regulation of oxidative stress-induced intrinsic apoptotic signaling pathway|
|negative regulation of oxidative stress-induced cell death|
|negative regulation of cellular response to oxidative stress|
|negative regulation of response to oxidative stress|
|E-box binding|
|regulation of oxidative stress-induced cell death|
|RNA polymerase II transcription factor complex|
|regulation of cellular response to oxidative stress|
|transcription regulatory region sequence-specific DNA binding|
|regulation of response to oxidative stress|
|negative regulation of intrinsic apoptotic signaling pathway|
|RNA polymerase II distal enhancer sequence-specific DNA binding|
|nuclear matrix|
|regulation of circadian rhythm|
|circadian rhythm|
|negative regulation of neuron apoptotic process|
|regulation of intrinsic apoptotic signaling pathway|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|DNA recombination|
|negative regulation of apoptotic signaling pathway|
|activation of innate immune response|
|rhythmic process|
|regulation of neuron death|
|positive regulation of innate immune response|
|positive regulation of response to biotic stimulus|
|chromatin binding|
|regulation of apoptotic signaling pathway|
|RNA splicing|
|nuclear speck|
|regulation of innate immune response|
|positive regulation of defense response|
|mRNA processing|
|negative regulation of intracellular signal transduction|
|positive regulation of multi-organism process|
|DNA repair|
|regulation of response to biotic stimulus|
|positive regulation of response to external stimulus|
|activation of immune response|
|mRNA metabolic process|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of defense response|
|innate immune response|
|cellular response to DNA damage stimulus|
|regulation of multi-organism process|
|nucleolus|
|positive regulation of immune response|
|RNA processing|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|defense response to other organism|
|negative regulation of cell death|
|identical protein binding|
|regulation of response to external stimulus|
|positive regulation of immune system process|
|regulation of immune response|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|negative regulation of signal transduction|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|negative regulation of RNA metabolic process|
|defense response|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|RNA binding|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|DNA-binding transcription factor activity, RNA polymerase II-specific|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|regulation of immune system process|
|RNA metabolic process|
|regulation of cell death|
|cellular response to stress|
|negative regulation of gene expression|
|regulation of intracellular signal transduction|
|immune response|
|membrane|
|gene expression|
\\
=== CRISPR Data ===
^Screen^Score^
|[[:results:exp21|MLN-4924 0.2μM R00 exp21]]|-2.94|
|[[:results:exp6|Bortezomib 0.005μM R00 exp6]]|-2.34|
|[[:results:exp517|Quercetin 20μM R08 exp517]]|-2.03|
|[[:results:exp134|MS023 2μM R03 exp134]]|-2|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|-1.88|
|[[:results:exp405|Tenofovir 10μM R07 exp405]]|-1.83|
|[[:results:exp502|Milciclib 2μM R08 exp502]]|-1.82|
|[[:results:exp497|Lead acetate 2000μM R08 exp497]]|-1.73|
|[[:results:exp66|BI-D1870 3.15μM R02 exp66]]|1.78|
|[[:results:exp34|Rotenone 20μM R00 exp34]]|1.78|
|[[:results:exp4|Actinomycin-D 0.01μM R00 exp4]]|1.86|
|[[:results:exp289|Hydroxyurea 15μM R06 exp289]]|2.11|
|[[:results:exp434|Vemurafenib 6.6μM R08 exp434]]|2.2|
|[[:results:exp89|Vemurafenib 6.6μM R02 exp89]]|2.52|
|[[:results:exp79|Q15 2.7μM R02 exp79]]|3.28|
No correlation found to any other genes in chemogenomics.
Global Fraction of Cell Lines Where Essential: 11/694
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/26|
|bone|0/26|
|breast|0/30|
|central nervous system|1/49|
|cervix|0/4|
|colorectal|1/17|
|esophagus|0/11|
|fibroblast|0/1|
|gastric|1/14|
|kidney|0/18|
|liver|1/19|
|lung|1/72|
|lymphocyte|0/16|
|ovary|0/25|
|pancreas|0/22|
|peripheral nervous system|1/15|
|plasma cell|0/12|
|prostate|0/1|
|skin|1/20|
|soft tissue|1/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/28|
|uterus|0/5|
== Essentiality in NALM6 ==
* **Essentiality Rank**: 4532
* **Expression level (log2 read counts)**: 9.23
{{:chemogenomics:nalm6 dist.png?nolink |}}