NONO (protein)

NONO
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3SDE
Identifiers
Aliases	NONO, NMT55, NRB54, P54, P54NRB, PPP1R114, MRXS34, non-POU domain containing, octamer-binding
External IDs	MGI: 1855692 HomoloGene: 7212 GeneCards: NONO
Gene ontology Molecular function • RNA polymerase II distal enhancer sequence-specific DNA binding • nucleotide binding • DNA binding • core promoter binding • chromatin binding • transcription regulatory region sequence-specific DNA binding • protein binding • identical protein binding • nucleic acid binding • RNA binding • poly(A) RNA binding Cellular component • paraspeckles • nuclear speck • membrane • nuclear matrix • nucleoplasm • RNA polymerase II transcription factor complex • nucleolus • nucleus Biological process • mRNA splicing, via spliceosome • DNA recombination • regulation of transcription, DNA-templated • rhythmic process • mRNA processing • transcription, DNA-templated • cellular response to DNA damage stimulus • regulation of circadian rhythm • circadian rhythm • RNA splicing • negative regulation of transcription, DNA-templated • negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway • DNA repair Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4841	53610
Ensembl	ENSG00000147140	ENSMUSG00000031311
UniProt	Q15233	Q99K48
RefSeq (mRNA)	NM_007363 NM_001145408 NM_001145409 NM_001145410	NM_001252518 NM_023144
RefSeq (protein)	NP_001138880.1 NP_001138881.1 NP_001138882.1 NP_031389.3	NP_001239447.1 NP_075633.2
Location (UCSC)	Chr X: 71.28 – 71.3 Mb	Chr X: 101.43 – 101.45 Mb
PubMed search	[1]	[2]
Wikidata

Non-POU domain-containing octamer-binding protein (NonO) is a protein that in humans is encoded by the nono gene.^[3][4][5]

The NonO protein belongs to the Drosophila behaviour/human splicing (DBHS) family of proteins.^[6] Proteins in the DHBS family include mammalian SFPQ (splicing factor, proline- and glutamine-rich; aka PSF), NONO (Non-POU domain-containing octamer-binding protein; aka p54nrb) and PSPC1 (paraspeckle component 1; aka PSP1) and invertebrate NONA (Protein no-on-transient A) and Hrp65.^[7]

Interactions

NONO has been shown to interact with SFPQ,^[8] SPI1^[9] and Androgen receptor.^[10]

Functions

NONO is involved with many nuclear processes and binds to both DNA and RNA.^[11]

As with all proteins of the DBHS familprotein is described as a multifunctional nuclear protein.^[12] 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.^{[11][13][14][15][16][17]}

NONO has been identified to bind with Rasd1 protein, in resulting dimer Rasd1 may act to modulate the function of NONO to down regulate the expression of the CREB genes, NR4A1 and Nr4A2.^[18]

NONO binds to SFPQ to form a heterodimer that interacts with the MATR3 protein.^[19] The interaction of these three proteins may be part of the process in the nucleus that is responsible for the retention of RNAs that are defective, not yet mature enough to be exported or are designed to be retained in nucleus.^[19]

Gene location

NONO protein (Human) is encoded by the NONO gene which is located on the plus strand of the X chromosome.^[20]

Role in disease

Melanoma

NONO has been shown to be more strongly expressed in melanoma cell lines and melanoma tissue samples compared to normal human cell lines and normal skin tissue.^[21] Studies have found that the knockout of NONO protein from melanoma cell lines results in both reduced proliferation rates of the cancer cells and a significant decrease in the potential migration of the cancer cells.^[21]

Breast cancer

Studies into breast cancers have found that the loss or alteration of NONO in conjunction with the loss of the estrogen receptor hERα results in more aggressive breast cancers which show an increase in both tumor size and metastases.^[22]

Intellectual disability

Studies in Humans and mice have identified that NONO null mutations likely lead to the development of a clinically recognizable intellectual disability with cognitive and affective deficits.^[23]

Structure

As with other proteins of the DBHS family, NONO protein functions rarely functions alone and primarily forms homo- and heterodimers with other DBHS proteins to perform its various functions.^[24] It is theorised that these dimers may have different functions that are specific to the type of cell that they are found in.^[25]

It is speculated that it is the phosphorylation state on NONO that acts to direct the proteins many disparate functions within the nucleus.^[11]

Tissue specificity

NONO is found in the nucleus of most mammalian cells and is primarily distributed within the nucleoplasm, it can also be found concentrated within sub-nuclear domains known as paraspeckles.^[26]

NONO has also been observed within the brain, localised in the cytoplasm of hippocampal neurons that are associated with RNA transport granules.^[27]

Discovery

NONO protein was first discovered in 1993 by researchers at Cold Springs Harbor Laboratory. Due to the protein being originally identified as a RNA-binding protein it was named p54nrb for Nuclear RNA-binding protein, 54 kDa.^[6]

References

Further reading

PDB gallery
2cpj: Solution structure of the N-terminal RNA recognition motif of NonO