| 1993 |
p54nrb was purified from HeLa cells and found to contain two RNA recognition motifs (RRMs). It shares 71% identity with splicing factor PSF within a 320 aa region including both RRMs, and both p54nrb and PSF define a novel conserved protein segment termed the DBHS domain (Drosophila behavior, human splicing), suggesting involvement in pre-mRNA splicing regulation. |
Protein purification, cDNA cloning, sequence analysis |
Nucleic acids research |
Medium |
8371983
|
| 1996 |
p54nrb was identified as a binding partner of the transcription factor Spi-1/PU.1 via an immobilized protein binding assay. Spi-1/PU.1 impedes the binding of p54nrb to RNA and alters the splicing process in vitro. |
Immobilized protein binding assay, in vitro splicing assay |
The Journal of biological chemistry |
Medium |
8626664
|
| 1997 |
p54nrb (NonO) was found fused to the TFE3 helix-loop-helix transcription factor gene in papillary renal cell carcinoma via an X chromosome inversion inv(X)(p11.2;q12), resulting in fusion of almost the entire splicing factor protein to the TFE3 DNA-binding domain. |
Cytogenetic and molecular analysis of tumor translocation/inversion |
Oncogene |
Medium |
9393982
|
| 1997 |
p54nrb was shown to bind to the IAP proximal enhancer (IPE) DNA element and to transactivate a reporter gene in HeLa cell extracts. The DNA-binding domain maps to the N-terminal half and the activation domain to the C-terminal half. p54nrb also binds pre-mRNA, demonstrating dual roles in transcription and splicing. |
Protein purification, reporter gene assay in cell extracts, domain mapping |
Molecular and cellular biology |
Medium |
9001221
|
| 2000 |
PSF/p54nrb stimulates DNA topoisomerase I to jump between separate DNA helices without affecting the cleavage or religation half-reactions themselves, suggesting PSF/p54nrb mobilizes topoisomerase I after ligation. |
In vitro topoisomerase I jumping assay with oligonucleotide substrates |
Biochemistry |
Medium |
10858305
|
| 2000 |
NonO/p54nrb was found to have carbonic anhydrase (CA) activity. Recombinant NonO generated in baculovirus bound to a CA inhibitor affinity column and revealed detectable CA activity (25 units/mg), identifying it as a nonclassical nuclear carbonic anhydrase. |
CA inhibitor affinity chromatography, CA activity measurements, recombinant protein expression in baculovirus |
The Journal of biological chemistry |
Medium |
10821857
|
| 2001 |
A multiprotein complex containing p54nrb, PSF, and matrin 3 binds specifically to inosine-containing (hyperedited) RNAs. This complex anchors hyperedited RNAs to the nuclear matrix, mediating their nuclear retention while allowing selectively edited mRNAs to be exported. |
HeLa nuclear extract fractionation, RNA affinity chromatography, Co-IP, nuclear matrix fractionation |
Cell |
High |
11525732
|
| 2001 |
p54nrb is cleaved/modified during Fas-induced apoptosis, as identified by 2D-gel proteome analysis of apoptotic Jurkat T cells with calculated caspase-3 cleavage sites. |
2D-PAGE proteomics, MALDI-TOF mass spectrometry, recombinant caspase-3 treatment |
The Journal of biological chemistry |
Low |
11352910
|
| 2001 |
PSF functions as a novel corepressor of nuclear hormone receptors (TR, RXR) by interacting with Sin3A and mediating silencing through recruitment of HDACs to the receptor DNA-binding domain. NonO/p54nrb was co-purified with PSF in this complex on TR and RXR, though p54nrb's independent contribution was not fully separated from PSF's. |
Biochemical purification, co-immunoprecipitation, reporter gene assay, in vivo studies with TR |
Molecular and cellular biology |
Medium |
11259580
|
| 2002 |
p54nrb localizes to a novel nuclear compartment termed paraspeckles (10–20 per cell), which are discrete bodies in the interchromatin nucleoplasmic space often adjacent to splicing speckles. p54nrb interacts dynamically with nucleoli in a transcription-dependent fashion and relocalizes to nucleolar cap structures when transcription is inhibited. |
Immunofluorescence, YFP-PSP1 stable cell line live imaging, FRAP, fluorescence microscopy |
Current biology : CB |
High |
11790299
|
| 2002 |
PSF and p54nrb/NonO bind specifically to the RNA polymerase II CTD (both hypo- and hyperphosphorylated forms) via affinity chromatography and co-immunoprecipitate with pol II holoenzyme. They can simultaneously interact with CTD and RNA, providing a physical link between pol II and pre-mRNA processing. |
CTD affinity chromatography, co-immunoprecipitation, RNA-binding assay |
RNA (New York, N.Y.) |
High |
12358429
|
| 2002 |
PSF and p54nrb interact with each other and bind U5 snRNA stem 1b via iterative selection and filter-binding assays. Both proteins associate with spliceosomes and the U4/U6.U5 tri-snRNP. |
RNA SELEX, filter-binding assay, RNA affinity selection, sedimentation analysis |
RNA (New York, N.Y.) |
Medium |
12403470
|
| 2002 |
p54nrb and PSF form complexes with SF-1 on the CYP17 promoter. The SF-1/PSF/p54nrb/NonO complex is required for cAMP-dependent transcriptional activation of the CYP17 gene. SF-1 co-immunoprecipitates with p54nrb indicating direct interaction. PSF-recruited mSin3A and HDAC activity mediates repression of basal transcription. |
EMSA, co-immunoprecipitation, luciferase reporter assay, trichostatin A treatment |
Endocrinology |
Medium |
11897684
|
| 2004 |
p54nrb associates with the 5' splice site within large complexes in HeLa cell nuclear extracts containing hyperphosphorylated RNA pol II (RNAPIIO) together with U1 or U1/U2 snRNPs, P-TEFb, TAT-SF1, TFIIF, PSF, and TLS. p54nrb and PSF can directly interact with the 5' splice site, suggesting they mediate contacts between RNAPII and snRNPs during coupled transcription/splicing. |
Nuclear extract fractionation, RNA-protein binding assay, immobilized DNA template assay |
The EMBO journal |
Medium |
15057275
|
| 2004 |
PSF and p54nrb form a stable heteromeric complex that reconstitutes efficient DNA double-strand break rejoining in vitro when added to the other five known NHEJ polypeptides. The PSF·p54nrb complex cooperates with Ku protein to form a functional preligation complex with substrate DNA. |
In vitro NHEJ reconstitution assay, complex purification |
The Journal of biological chemistry |
High |
15590677
|
| 2005 |
p54nrb forms a heterodimer with PSP1 in vivo, and this interaction requires a specific domain within PSP1. The PSP1-p54nrb interaction is necessary but not sufficient for PSP1 paraspeckle targeting, which also requires an RNA-binding-capable RRM. Paraspeckle formation depends on RNA Pol II transcription. |
Co-immunoprecipitation, domain mapping by truncation mutants, DRB transcription inhibition, fluorescence microscopy |
Molecular biology of the cell |
High |
16148043
|
| 2005 |
p54nrb is multiphosphorylated during mitosis. CDK1 (identified via roscovitine inhibition and cyclin B1 immunodepletion) phosphorylates the C-terminal extremity of p54nrb. A different kinase phosphorylates the N-terminal region. p54nrb interacts with the peptidylprolyl isomerase Pin1 via three C-terminal threonine residues, with binding favored when at least two are phosphorylated, suggesting regulation by phosphorylation-dependent conformational changes. |
Phospho-specific antibody staining, CDK inhibitor treatment, immunodepletion, site-directed mutagenesis, Pin1 interaction assay |
Journal of molecular biology |
High |
15701524
|
| 2005 |
PSF and p54nrb preferentially bind strong transcriptional activation domains and preferentially bind the full-length pol II CTD (52 repeats) rather than a truncated 15-repeat CTD. Elevated PSF expression bypasses the requirement for a strong activator for efficient splicing and 3'-end cleavage. PSF/p54nrb-dependent stimulation of splicing primarily affects first intron removal. |
Affinity chromatography, transfection/overexpression, reporter assay, CTD truncation mutants |
Molecular and cellular biology |
Medium |
16024807
|
| 2006 |
p54nrb is a component of the snRNP-free U1A (SF-A) complex that also contains PSF and p68. Immunodepletion of p54nrb followed by reconstitution experiments showed that p54nrb is critical for pre-mRNA cleavage during polyadenylation. |
TAP purification, mass spectrometry, immunodepletion, reconstitution, in vitro polyadenylation assay |
RNA (New York, N.Y.) |
High |
16373496
|
| 2006 |
Nuclear N-WASP exists in a large nuclear complex containing PSF-NonO/p54nrb, nuclear actin, and RNA polymerase II. The interaction of N-WASP with the PSF-NonO complex couples N-WASP to RNA pol II to regulate transcription. N-WASP-mediated nuclear actin polymerization contributes to this regulation. |
Co-immunoprecipitation, nuclear complex purification, transcription reporter assay |
Nature cell biology |
Medium |
16767080
|
| 2007 |
p54nrb/NonO is required for cAMP-dependent activation of CREB target genes in vivo. TORC2 and NONO complex on cAMP-responsive promoters, and NONO acts as a bridge between the CREB/TORC complex and RNA polymerase II. |
High-throughput coactivator trap screen, RNAi knockdown, chromatin immunoprecipitation (ChIP) |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
18077367
|
| 2007 |
p54nrb/NonO physically associates with XRN2 via PSF/p54nrb acting as a bridge. p54nrb is present along the length of genes, is required for degradation of the 3'-cleaved RNA downstream of the poly(A) site in vitro, and its siRNA knockdown leads to defects in XRN2 recruitment and transcription termination in vivo. |
Co-immunoprecipitation, in vitro 3' processing assay, siRNA knockdown, ChIP |
Genes & development |
High |
17639083
|
| 2007 |
PSF and p54nrb bind RNAs containing AU-rich elements (AREs), including the TNFα mRNA. PSF is phosphorylated by Mnk kinases at two sites in vitro and in vivo, and Mnk-mediated phosphorylation increases the binding of PSF to TNFα mRNA in living cells. |
In vitro kinase assay, mass spectrometry, RNA immunoprecipitation (RIP), cap-resin pulldown |
The Journal of biological chemistry |
Medium |
17965020
|
| 2007 |
p54nrb and PSF interact with the two COX-2 upstream sequence elements (USEs). Tethering p54nrb to COX-2 USE mutant RNA compensates for the cis-acting elements in polyadenylation. p54nrb, PTB, PSF, and U1A may interact as a complex since co-immunoprecipitation of MS2 fusion proteins coprecipitates the other partners. |
RNA pulldown with biotinylated oligonucleotides, MS2 tethering assay, co-immunoprecipitation |
RNA (New York, N.Y.) |
Medium |
17507659
|
| 2007 |
p54nrb physically interacts with Sox9 and enhances Sox9-dependent transcriptional activation of the Col2a1 promoter. p54nrb colocalizes with Sox9 in nuclear paraspeckle bodies in ATDC5 cells. A p54nrb mutant lacking RNA recognition motifs dominantly inhibits Col2a1 mRNA maturation, chondrocyte differentiation in vitro and in mesenchymal explants, and causes dwarfism in transgenic mice. |
Co-immunoprecipitation, reporter assay, dominant-negative RRM mutant overexpression, transgenic mouse model, RNA maturation assay |
The Journal of clinical investigation |
High |
18677406
|
| 2008 |
p54nrb binds both BRG1 and Brm (catalytic subunits of the SWI/SNF complex) and the core subunit BAF60a. The N-terminal region of p54nrb is sufficient to pull down other SWI/SNF core subunits. Brm in concert with p54nrb co-localizes at a TERT alternative splicing acceptor site and modulates TERT splicing (promoting exon-inclusion) and transcription. |
Pulldown assay, co-immunoprecipitation, shRNA knockdown, ChIP, RT-PCR splicing analysis |
The Biochemical journal |
Medium |
18042045
|
| 2008 |
mRNAs containing inverted Alu repeats in their 3'-UTR are retained in the nucleus and associate with p54nrb in a manner that correlates with A-to-I RNA editing. The Nicolin 1 mRNA isoform containing inverted Alu repeats is retained in the nucleus while the isoform lacking these sequences is exported, identifying p54nrb as a component of a gene silencing mechanism mediated by Alu elements. |
EGFP reporter assay, nuclear/cytoplasmic fractionation, RNA immunoprecipitation |
The EMBO journal |
Medium |
18497743
|
| 2009 |
p54nrb/PSF and PSP1 are expressed in human embryonic stem cells but paraspeckles are absent; paraspeckle assembly requires NEAT1 lncRNA expression, which is absent in hESCs and induced upon differentiation. Knockdown of NEAT1 in HeLa cells results in loss of paraspeckles and enhanced cytoplasmic export of mRNAs containing inverted Alu repeats. |
siRNA knockdown of NEAT1, immunofluorescence, nuclear/cytoplasmic fractionation, hESC differentiation |
Molecular cell |
High |
19716791
|
| 2009 |
p54/nrb and PSF selectively associate with and stabilize the longer MENbeta (NEAT1_2) lncRNA isoform among the two paraspeckle ncRNAs (MENepsilon/MENbeta), contributing to paraspeckle structural organization. Removal of MENepsilon/beta by knockdown results in paraspeckle disintegration. |
RNA immunoprecipitation, siRNA knockdown, immunofluorescence |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19188602
|
| 2009 |
p54nrb contributes to rapid and accurate repair of DNA double-strand breaks in vivo. siRNA-mediated p54nrb knockdown delays DSB repair (gamma-H2AX focus assay) and stable miRNA knockdown cell lines show increased ionizing radiation-induced chromosomal aberrations and increased radiosensitivity in clonogenic assay. |
siRNA/miRNA knockdown, gamma-H2AX focus assay, clonogenic survival assay, chromosomal aberration analysis |
Nucleic acids research |
High |
19759212
|
| 2009 |
p54nrb interacts with hnRNP M via co-immunoprecipitation and pulldown assays, co-localizes with PSF in a subset of nuclear paraspeckles, and co-fractionates with PSF and p54nrb in the nuclear matrix. PSF and hnRNP M have opposing effects on alternative splicing: hnRNP M promotes exon skipping while PSF favors inclusion, and their antagonism requires hnRNP M domains capable of interacting with PSF/p54nrb. |
Co-immunoprecipitation, pulldown, immunofluorescence, nuclear matrix fractionation, PPT minigene splicing assay |
Experimental cell research |
Medium |
19874820
|
| 2009 |
p54nrb is a transcriptional corepressor of the progesterone receptor (PR) independent of PSF. p54nrb interacts directly with PR in a ligand-independent manner. p54nrb recruits mSin3A through its N-terminus to the PR-DNA complex, resulting in inhibition of PR-mediated transactivation. Knockdown of p54nrb alleviates PR-mediated repression on connexin 43 (Gja1) transcription. |
Co-immunoprecipitation, luciferase reporter assay, ChIP, siRNA knockdown, site-directed mutagenesis |
Molecular endocrinology (Baltimore, Md.) |
High |
19423654
|
| 2011 |
Mitotic CDK1-mediated phosphorylation of p54nrb reduces its general RNA-binding ability. In vitro CDK1 phosphorylation of GST-p54nrb abolishes interaction with 5' splice site RNA and homoribopolymers poly(A), poly(C), and poly(U) but not poly(G). Threonine 15 (N-terminal to the tandem RRM domains) is required for this inhibition by mutagenesis. Neat1 ncRNA co-immunoprecipitates with p54nrb in both interphase and mitotic cells, indicating that p54nrb-Neat1 interaction is not modulated by phosphorylation. |
In vitro kinase assay (CDK1), RNA binding assay, site-directed mutagenesis (T15), co-immunoprecipitation, cell synchronization |
Biochemistry and cell biology |
High |
21819346
|
| 2011 |
PP1 forms a protein complex with p54nrb and PSF, interacting directly with p54nrb via its RVxF motif. PP1 association results in dephosphorylation of p54nrb and PSF, leading to loss of their transcriptional corepressor activities and altered alternative splicing activities (shifting from exon inclusion to exon skipping). Dephosphorylation changes p54nrb/PSF interactions with Sin3A, HDAC1, U1A and U2AF. |
Co-immunoprecipitation, RVxF motif mutagenesis, luciferase reporter assay, CD44 minigene splicing assay, in vivo phosphorylation analysis |
Molecular endocrinology (Baltimore, Md.) |
High |
21566083
|
| 2012 |
p54nrb forms a complex with ILF3 that binds to the survivin promoter to regulate survivin expression. The small molecule YM155 binds ILF3 and disrupts the ILF3/p54nrb complex, resulting in different subcellular localization of the two proteins and suppression of survivin expression. |
Co-immunoprecipitation, ChIP, immunofluorescence localization, YM155 treatment |
Biochemical and biophysical research communications |
Medium |
22842455
|
| 2013 |
NonO/p54nrb binds to the rhodopsin distal enhancer region (RER) as validated by ChIP-seq showing high NonO occupancy at rhodopsin and phototransduction genes. NonO and its interactors (hnRNP M, Ywhaz, Ppp1ca) activate the rhodopsin promoter in HEK293 cells synergistically with NRL and CRX; the DNA-binding domain of NonO is critical. shRNA knockdown of NonO in mouse retina leads to loss of rhodopsin expression, rod cell death, splicing defects, and altered expression of phototransduction genes. |
Mass spectrometry identification, co-immunoprecipitation, ChIP-seq, luciferase reporter assay, shRNA knockdown in retina, RNA-seq |
Human molecular genetics |
High |
24301678
|
| 2013 |
During apoptosis induced by TRAIL, PTB forms a remodeled complex with PSF and NONO/p54nrb among others. Increased expression of NONO/p54nrb accelerates apoptosis. These proteins post-transcriptionally regulate apoptosis rates by interacting with and stimulating IRES activity in mRNAs translated during apoptosis. |
Co-immunoprecipitation, overexpression/knockdown with apoptosis rate measurement, IRES reporter assay |
Cell death and differentiation |
Medium |
24141718
|
| 2014 |
p54nrb/NonO and PSF promote U snRNA nuclear export by accelerating assembly of the U snRNA export complex. As a heterodimer, they accelerate the recruitment of PHAX, and subsequently CRM1 and Ran, onto RNA substrates in vitro, mediating efficient U snRNA export in vivo. |
In vitro U snRNA export complex assembly assay, microinjection/in vivo export assay |
Nucleic acids research |
Medium |
24413662
|
| 2015 |
CARM1 (coactivator-associated arginine methyltransferase 1) methylates the coiled-coil domain of p54nrb, resulting in reduced binding of p54nrb to mRNAs containing inverted Alu repeats (IRAlus). CARM1 also suppresses NEAT1 transcription to reduce paraspeckle formation. Both mechanisms together promote nuclear export of IRAlu-containing mRNAs, especially under poly(I:C) stress. |
Co-immunoprecipitation, in vitro methylation assay, RNA immunoprecipitation, NEAT1 knockdown, poly(I:C) treatment, nuclear/cytoplasmic fractionation |
Genes & development |
High |
25792598
|
| 2015 |
The SFPQ·NONO native complex purified from HeLa cells binds DNA independently of free ends (unlike Ku), has DNA pairing activity in a microwell assay, and stimulates DNA-dependent protein kinase (DNA-PKcs) autophosphorylation. These findings suggest SFPQ·NONO promotes end joining by binding internal DNA sequences and stabilizing a synaptic pre-ligation complex without occluding DNA termini. |
Native complex purification from HeLa cells, microwell-based DNA binding/pairing assay, DNA-PK autophosphorylation assay |
Biochemical and biophysical research communications |
Medium |
25998385
|
| 2015 |
p54nrb/NONO binds the nuclear form of SREBP-1a, and the conserved Y267 residue of p54nrb is required for this interaction. p54nrb binding to nuclear SREBP-1a increases its protein stability, stimulating SREBP-1-mediated transcription of lipogenic genes and lipid production in breast cancer cells. |
Co-immunoprecipitation, site-directed mutagenesis (Y267), reporter assay, in vitro and in vivo tumor growth assays |
Oncogene |
Medium |
26148231
|
| 2015 |
p54nrb/NONO regulates glucocorticoid production by modulating the splicing of multiple phosphodiesterase (PDE) isoforms and facilitating the interaction between XRN2 and select PDE transcripts to regulate their stability. Silencing p54nrb in H295R adrenocortical cells decreases cAMP production and cortisol biosynthesis in response to ACTH. |
siRNA knockdown, RT-PCR splicing analysis, RNA stability assay, co-immunoprecipitation |
Molecular and cellular biology |
Medium |
25605330
|
| 2015 |
p54nrb/NONO transcriptionally regulates the lncRNA PCGEM1 by binding its promoter in response to androgen deprivation. Suppression of p54nrb reduces PCGEM1, and re-expression restores it. DIM (3,3'-diindolylmethane) suppresses PCGEM1 by preventing the interaction of p54nrb with the PCGEM1 promoter. |
siRNA/CRISPR KO, rescue experiments, ChIP showing p54nrb on PCGEM1 promoter |
Scientific reports |
Medium |
27682980
|
| 2016 |
Progesterone-liganded nuclear PRB forms a complex including JUN/JUN homodimers and P54nrb/Sin3A/HDAC to repress transcription of the labor gene Cx43. Unliganded PRA paradoxically activates Cx43 transcription. Increased 20α-HSD expression reduces nuclear progesterone levels during labor, switching PR from liganded to unliganded state. |
Co-immunoprecipitation, ChIP, reporter assay, siRNA knockdown, immunofluorescence |
Nature communications |
Medium |
27220952
|
| 2016 |
The structure of p54nrb/NonO RRM1 was determined by NMR, revealing a canonical fold (β1α1β2β3α2β4) with conserved aromatic amino acids. Only RRM1 (not RRM2) binds to 5' splice site RNA. The binding interface was mapped by NMR and the affinity was determined by fluorescence quenching. Phosphorylation of T15 (N-terminal to RRM1) inhibits RNA binding except for G-rich RNAs. |
NMR structure determination, fluorescence quenching binding assay, in vitro RNA binding |
Biochemistry |
High |
27064654
|
| 2016 |
Crystal structure of NONO homodimer was obtained at 2.6 Å resolution by molecular replacement. NONO crystallizes as a superhelical arrangement of six NONO homodimers, establishing that NONO is an obligatory homodimer. L-proline stabilizes purified NONO homodimers and prevents aggregation. |
X-ray crystallography, SAXS |
Acta crystallographica. Section D, Structural biology |
High |
27303796
|
| 2016 |
Tyrosine residues of p54nrb are not phosphorylated (p54nrb shows non-specific binding to anti-phosphotyrosine antibodies). However, replacement of tyrosine residues with phenylalanine altered p54nrb activities in transcriptional co-repression and RNA splicing in a gene context-dependent manner by differentially regulating p54nrb protein associations with interacting partners. |
Site-directed mutagenesis (Y-to-F substitutions), luciferase reporter assay, minigene splicing assay, co-immunoprecipitation, confocal microscopy |
Journal of cellular physiology |
Medium |
27430900
|
| 2017 |
NEAT1 depletion releases sequestered P54nrb and PSF from paraspeckles to facilitate IRES-dependent translation of c-Myc mRNA. Increased association of P54nrb and PSF with c-Myc mRNA was observed in NEAT1-depleted cells under RNAP I inhibition (CX5461 treatment). |
Antisense oligonucleotide-mediated NEAT1 knockdown, RNA immunoprecipitation (RIP), immunofluorescence |
PloS one |
Medium |
28288210
|
| 2018 |
CARM1 accumulates in nuclear granules (mostly paraspeckles) at the 2- to 4-cell stage of mouse embryo development. The paraspeckle component NEAT1 and its partner p54nrb are required for CARM1's association with paraspeckles and for H3R26 methylation. Conversely, CARM1 influences paraspeckle organization. Depletion of p54nrb results in arrest at the 16- to 32-cell stage with elevated Cdx2, indicating that paraspeckles (with p54nrb as a component) act upstream of CARM1 in early embryo cell fate determination. |
Immunofluorescence in mouse embryos, p54nrb depletion (siRNA/morpholino), H3R26 methylation analysis, developmental arrest assay |
Cell |
High |
30550788
|
| 2019 |
P54nrb interacts with RNase H1 via its core domains; toxic phosphorothioate antisense oligonucleotides (PS-ASOs) form a complex that includes RNase H1, P54nrb, and PSF (but safe PS-ASOs do not). P54nrb RRM1 and RRM2 are required for PS-ASO binding. The protein-protein interaction between P54nrb and RNase H1 requires the spacer region of RNase H1. RNA is also a required component of this complex. |
NanoLuciferase structural complementation reporter (real-time in live cells), in vitro binding assay, domain deletion analysis |
Nucleic acids research |
Medium |
31495875
|
| 2020 |
NONO promotes BIN1 exon 12a inclusion (oncogenic splicing switch) through interaction with DHX9 and SFPQ forming a DHX9-NONO-SFPQ complex. Knockdown of NONO abolishes liver cancer cell proliferation, migration, and BIN1-L expression, while BIN1-L stabilizes PLK1 by preventing cullin 3-mediated ubiquitination. |
RNA-seq, co-immunoprecipitation, siRNA knockdown, minigene splicing assay, tumor formation assay |
Hepatology (Baltimore, Md.) |
Medium |
31815296
|
| 2020 |
SFPQ, in complex with p54nrb, binds and regulates the activity of splicing factor SRSF2 under platinum treatment. The SFPQ/p54nrb complex decreases SRSF2 binding to caspase-9 RNA, favoring expression of the antiapoptotic caspase-9b isoform and contributing to chemoresistance. |
Co-immunoprecipitation, RNA immunoprecipitation, siRNA knockdown, alternative splicing analysis |
Oncogene |
Medium |
32332923
|
| 2021 |
NONO interacted with and stabilized both HIF-1α and HIF-2α complexes, activating transcription of hypoxia-induced genes. NONO also bound pre-mRNA and mature mRNA of HIF-1/2 targets to facilitate splicing and mRNA stability. NONO knockout disrupted expression of HIF-1/2 targets and impeded hypoxia-enhanced progression in hepatocellular carcinoma. |
Co-immunoprecipitation, RNA immunoprecipitation, NONO knockout, in vitro/in vivo tumor assays, ChIP |
Oncogene |
Medium |
34079086
|
| 2022 |
p54nrb is a substrate of caspase-2, which cleaves p54nrb at D422, disrupting its C-terminal DNA-binding region. Loss or cleavage of p54nrb results in altered expression of oncogenic genes including cathepsin-Z and gelsolin. p54nrb interacts with cathepsin-Z and gelsolin DNA (but not RNA). Loss of p54nrb increases cell death susceptibility in tumor cell lines. |
In vitro caspase-2 cleavage assay, quantitative proteomics, ChIP (DNA interaction), siRNA/CRISPR knockdown/KO, cell death assay |
Cell death & disease |
Medium |
35444189
|
| 2022 |
Lysine 371 of p54nrb is reversibly acetylated: acetyltransferase GCN5 acetylates K371, and deacetylase SIRT1 removes the modification. GCN5-mediated acetylation attenuates recruitment of p54nrb to its core binding motif within the IL-8 gene promoter, increasing IL-8 expression; SIRT1-mediated deacetylation reverses this. |
Site-directed mutagenesis (K371), co-immunoprecipitation, ChIP, luciferase reporter assay, in vitro acetylation assay |
Biochemical and biophysical research communications |
Medium |
35843094
|
| 2022 |
p54nrb/NONO significantly interacted with nuclear EGFR in triple-negative breast cancer. NONO increased the stability of nuclear EGFR and recruited CBP/p300, enhancing EGFR transcriptional activity. In turn, EGFR positively regulated NONO's affinity to mRNAs of EGFR downstream genes. |
Co-immunoprecipitation, proximity ligation assay, siRNA knockdown, reporter assay, protein stability assay |
Cell death & disease |
Medium |
35013116
|
| 2022 |
Paraspeckle proteins p54nrb and PSPC1 function as IRES trans-acting factors (ITAFs) for subgroups of (lymph)angiogenic and cardioprotective factor mRNAs during hypoxia. NEAT1 and IRES-containing mRNAs are recruited into paraspeckles during hypoxia. Paraspeckles act as a platform for IRESome assembly and IRES-dependent translation. |
siRNA knockdown, polysome profiling, smiFISH for mRNA localization, mass spectrometry, IRES reporter assay |
eLife |
Medium |
36546462
|
| 2024 |
Nono deletion in murine KP lung cancer cells impairs the DNA damage response to etoposide and bleomycin, with hyperactivation of DSB signaling, reduced RNA pol II promoter occupancy, impaired nascent RNA synthesis, and attenuated induction of Gadd45b. Gadd45b is identified as a putative Nono-dependent effector of the DDR, indicating Nono mediates a genome-protective crosstalk between the DDR and RNA metabolism. |
CRISPR/Cas9 Nono deletion, gamma-H2AX assay, Pol II ChIP, nascent RNA synthesis assay, RT-PCR/Western blot for Gadd45b |
Life science alliance |
Medium |
38843934
|
| 2025 |
GYS1 (glycogen synthase 1) complexes with NONO/p54nrb in the nucleus and undergoes liquid-liquid phase separation with NONO to form nuclear condensates, leading to GYS1 nuclear retention and inhibition of glycogen biosynthesis. NONO and nGYS1 co-condense with MyoD and preinitiation complex (PIC) proteins to form transcriptional condensates, driving myogenic gene expression. Nono-deficient mice exhibit exercise intolerance, higher muscle glycogen content, smaller myofibers, and impaired muscle regeneration. |
Co-immunoprecipitation, FRAP, in vitro phase separation assay, Nono knockout mice, C2C12 differentiation assay, cardiotoxin muscle regeneration model, ChIP |
Cell death and differentiation |
Medium |
40200092
|