NONO (protein)

This article is about non-POU domain-containing octamer-binding protein coding gene. For other uses, see nono (disambiguation).
NONO
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
Aliases NONO, NMT55, NRB54, P54, P54NRB, PPP1R114, MRXS34, non-POU domain containing, octamer-binding
External IDs MGI: 1855692 HomoloGene: 7212 GeneCards: NONO
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
View/Edit HumanView/Edit Mouse

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

  1. ↑ "Human PubMed Reference:".
  2. ↑ "Mouse PubMed Reference:".
  3. ↑ Dong B, Horowitz DS, Kobayashi R, Krainer AR (August 1993). "Purification and cDNA cloning of HeLa cell p54nrb, a nuclear protein with two RNA recognition motifs and extensive homology to human splicing factor PSF and Drosophila NONA/BJ6". Nucleic Acids Research. 21 (17): 4085–92. doi:10.1093/nar/21.17.4085. PMC 310009Freely accessible. PMID 8371983.
  4. ↑ Traish AM, Huang YH, Ashba J, Pronovost M, Pavao M, McAneny DB, Moreland RB (August 1997). "Loss of expression of a 55 kDa nuclear protein (nmt55) in estrogen receptor-negative human breast cancer". Diagnostic Molecular Pathology. 6 (4): 209–21. doi:10.1097/00019606-199708000-00005. PMID 9360842.
  5. ↑ "Entrez Gene: NONO Non-POU domain containing, octamer-binding".
  6. 1 2 Dong B, Horowitz DS, Kobayashi R, Krainer AR (August 1993). "Purification and cDNA cloning of HeLa cell p54nrb, a nuclear protein with two RNA recognition motifs and extensive homology to human splicing factor PSF and Drosophila NONA/BJ6". Nucleic Acids Research. 21 (17): 4085–92. PMID 8371983.
  7. ↑ Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH, Bond CS (March 2012). "Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body about a formation of nonos taking of the world lallalal everybody loves nono". Proceedings of the National Academy of Sciences of the United States of America. 109 (13): 4846–50. doi:10.1073/pnas.1120792109. PMID 22416126.
  8. ↑ Peng R, Dye BT, Pérez I, Barnard DC, Thompson AB, Patton JG (October 2002). "PSF and p54nrb bind a conserved stem in U5 snRNA". Rna. 8 (10): 1334–47. doi:10.1017/S1355838202022070. PMC 1370341Freely accessible. PMID 12403470.
  9. ↑ Hallier M, Tavitian A, Moreau-Gachelin F (May 1996). "The transcription factor Spi-1/PU.1 binds RNA and interferes with the RNA-binding protein p54nrb". The Journal of Biological Chemistry. 271 (19): 11177–81. doi:10.1074/jbc.271.19.11177. PMID 8626664.
  10. ↑ Ishitani K, Yoshida T, Kitagawa H, Ohta H, Nozawa S, Kato S (July 2003). "p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor". Biochemical and Biophysical Research Communications. 306 (3): 660–5. doi:10.1016/S0006-291X(03)01021-0. PMID 12810069.
  11. 1 2 3 "PSF and p54nrb/NonO – multi-functional nuclear proteins".
  12. ↑ Duvignaud JB, Bédard M, Nagata T, Muto Y, Yokoyama S, Gagné SM, Vincent M (May 2016). "Structure, Dynamics, and Interaction of p54(nrb)/NonO RRM1 with 5' Splice Site RNA Sequence". Biochemistry. 55 (18): 2553–66. doi:10.1021/acs.biochem.5b01240. PMID 27064654.
  13. ↑ Basu A, Dong B, Krainer AR, Howe CC (February 1997). "The intracisternal A-particle proximal enhancer-binding protein activates transcription and is identical to the RNA- and DNA-binding protein p54nrb/NonO". Molecular and Cellular Biology. 17 (2): 677–86. PMC 231793Freely accessible. PMID 9001221.
  14. ↑ Danckwardt S, Kaufmann I, Gentzel M, Foerstner KU, Gantzert AS, Gehring NH, Neu-Yilik G, Bork P, Keller W, Wilm M, Hentze MW, Kulozik AE (June 2007). "Splicing factors stimulate polyadenylation via USEs at non-canonical 3' end formation signals". The EMBO Journal. 26 (11): 2658–69. doi:10.1038/sj.emboj.7601699. PMID 17464285.
  15. ↑ Hallier M, Lerga A, Barnache S, Tavitian A, Moreau-Gachelin F (February 1998). "The transcription factor Spi-1/PU.1 interacts with the potential splicing factor TLS". The Journal of Biological Chemistry. 273 (9): 4838–42. doi:10.1074/jbc.273.9.4838. PMID 9478924.
  16. ↑ Kameoka S, Duque P, Konarska MM (April 2004). "p54(nrb) associates with the 5' splice site within large transcription/splicing complexes". The EMBO Journal. 23 (8): 1782–91. doi:10.1038/sj.emboj.7600187. PMC 394241Freely accessible. PMID 15057275.
  17. ↑ Kowalska E, Ripperger JA, Hoegger DC, Bruegger P, Buch T, Birchler T, Mueller A, Albrecht U, Contaldo C, Brown SA (January 2013). "NONO couples the circadian clock to the cell cycle". Proceedings of the National Academy of Sciences of the United States of America. 110 (5): 1592–9. doi:10.1073/pnas.1213317110. PMID 23267082.
  18. ↑ Ong SA, Tan JJ, Tew WL, Chen KS (2011-01-01). "Rasd1 modulates the coactivator function of NonO in the cyclic AMP pathway". PloS One. 6 (9): e24401. doi:10.1371/journal.pone.0024401. PMID 21915321.
  19. 1 2 Zhang Z, Carmichael GG (August 2001). "The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs". Cell. 106 (4): 465–75. PMID 11525732.
  20. ↑ "NONO - Non-POU domain-containing octamer-binding protein - Homo sapiens (Human) - NONO gene & protein". www.uniprot.org. Retrieved 2016-10-14.
  21. 1 2 Schiffner S, Zimara N, Schmid R, Bosserhoff AK (August 2011). "p54nrb is a new regulator of progression of malignant melanoma". Carcinogenesis. 32 (8): 1176–82. doi:10.1093/carcin/bgr103. PMID 21642354.
  22. ↑ Pavao M, Huang YH, Hafer LJ, Moreland RB, Traish AM (2001-01-01). "Immunodetection of nmt55/p54nrb isoforms in human breast cancer". BMC Cancer. 1: 15. doi:10.1186/1471-2407-1-15. PMID 11710964.
  23. ↑ Mircsof D, Langouët M, Rio M, Moutton S, Siquier-Pernet K, Bole-Feysot C, et al. (December 2015). "Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects". Nature Neuroscience. 18 (12): 1731–6. doi:10.1038/nn.4169. PMID 26571461.
  24. ↑ Fox AH, Bond CS, Lamond AI (November 2005). "P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner". Molecular Biology of the Cell. 16 (11): 5304–15. doi:10.1091/mbc.E05-06-0587. PMID 16148043.
  25. ↑ Knott GJ, Bond CS, Fox AH (May 2016). "The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold". Nucleic Acids Research. 44 (9): 3989–4004. doi:10.1093/nar/gkw271. PMID 27084935.
  26. ↑ Fox AH, Lamond AI (July 2010). "Paraspeckles". Cold Spring Harbor Perspectives in Biology. 2 (7): a000687. doi:10.1101/cshperspect.a000687. PMID 20573717.
  27. ↑ Kanai Y, Dohmae N, Hirokawa N (August 2004). "Kinesin transports RNA: isolation and characterization of an RNA-transporting granule". Neuron. 43 (4): 513–25. doi:10.1016/j.neuron.2004.07.022. PMID 15312650.

Further reading

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