| 1993 |
RBMX (hnRNP G/p43) is an RNA-binding protein that is O-linked N-acetylglucosamine glycosylated, contains an RNP-consensus RNA binding domain (RBD) at the amino terminus, and a carboxyl domain rich in serines, arginines, and glycines. |
cDNA cloning, sequencing, glycosylation characterization |
Nucleic acids research |
High |
7692398
|
| 2000 |
RBMX (hnRNP G) interacts with Tra2beta (an SR-like splicing factor) via protein-protein interaction; endogenous hnRNP G and Tra2beta are associated in HeLa nuclear extracts; phosphorylation enhanced the interaction and reduced competing RNA binding; the protein interaction domain of RBM inhibited splicing in vitro of a pre-mRNA substrate containing a Tra2beta-bound enhancer. |
Co-immunoprecipitation of endogenous proteins, in vitro splicing assay, phosphorylation assay |
Human molecular genetics |
High |
10749975
|
| 2002 |
RBMX (hnRNP G) promotes inclusion of SMN2 exon 7 by directly and specifically binding to Htra2-beta1 (an SR-like splicing factor); this protein-protein interaction (rather than non-specific RNA binding) mediates exon 7 inclusion; recombinant hnRNP G increases endogenous SMN protein levels. |
In vivo splicing assays, direct protein-protein interaction assays, deletion mutant analysis |
Human molecular genetics |
High |
12165565
|
| 2003 |
RBMX (hnRNP G) and hTra2beta have opposing effects on exon inclusion/exclusion; hnRNP G acts via a specific sequence to repress the skeletal muscle-specific exon (SK) of TPM3 and stimulates inclusion of the non-muscle exon; binding of hnRNP G to the exon is antagonized by hTra2beta; both proteins have opposite effects on a dystrophin pseudo-exon linked to X-linked dilated cardiomyopathy. |
Mini-gene transfection splicing assays, co-transfection in cardiac and skeletal myoblasts |
Human molecular genetics |
High |
12761049
|
| 2007 |
RBMX (hnRNP G) forms a complex with ZAP3, PP1, SAM68, CIA, and NF110/45; the interaction of hnRNP G with ZAP3 is lost upon digestion of endogenous nucleic acid, indicating RNA-dependent interaction. |
Proteomic analysis of ZAP3 complex, co-immunoprecipitation, nucleic acid digestion |
Biochimica et biophysica acta |
Medium |
17890166
|
| 2008 |
RBMX (hnRNP G) binds and transactivates the Txnip tumor suppressor promoter in vivo; a K22R mutation in the RBD abolishes this transcriptional activity; overexpression of Txnip alone inhibits anchorage-independent growth, linking RBMX tumor suppression to Txnip upregulation. |
Chromatin immunoprecipitation (ChIP), promoter reporter assays, site-directed mutagenesis, anchorage-independent growth assay |
Biochemical and biophysical research communications |
Medium |
18541147
|
| 2008 |
RBMX is required for normal anterior neural plate patterning, neurogenesis, neural crest development, and muscle segmentation in Xenopus; morpholino-mediated knockdown causes these specific developmental defects. |
Morpholino knockdown in Xenopus laevis embryos, expression cloning screen |
Developmental dynamics |
Medium |
18521943
|
| 2008 |
RBMX associates with ARTS-1 via co-immunoprecipitation; RNAi depletion of RBMX reduces both constitutive release of TNFR1 exosome-like vesicles and IL-1β-mediated proteolytic cleavage of TNFR1 ectodomains; conversely, RBMX overexpression increases both pathways of TNFR1 release. |
Co-immunoprecipitation, RNA interference, ELISA for TNFR1 shedding, overexpression |
Biochemical and biophysical research communications |
Medium |
18445477
|
| 2009 |
RBMX (hnRNP G) activates the testis-specific TLE4-T cassette exon by directly binding pre-mRNA sequences around this exon as a splicing co-activator; a high-affinity binding site for hnRNP G-T (the germ cell paralog) was also identified, showing sequence-specific RNA binding. |
RNA pull-down, mini-gene splicing assays, co-expression with Tra2beta, identification of binding site |
PLoS genetics |
High |
19893608
|
| 2009 |
RBMX interacts with SAFB1; both SAFB1 and RBMX bind to the upstream region of the Srebp-1c gene promoter (by ChIP); SAFB1 knockdown reduces RBMX-induced Srebp-1c promoter activity, and SAFB1 overexpression only affects Srebp-1c promoter in the presence of RBMX. |
Yeast two-hybrid, immunoprecipitation, chromatin immunoprecipitation (ChIP), RNA interference, reporter assays |
BMB reports |
Medium |
19403048
|
| 2010 |
RBMX (hnRNP G) has a modular domain organization: the RRM is not required for recruitment to nascent transcripts; a centrally positioned Nascent Transcripts Targeting Domain (NTD, residues 186-236) acts autonomously to target hnRNP G to active transcription units; an additional auxiliary C-terminal RNA Binding Domain (RBD, 58 residues) recognizes a hairpin RNA motif. |
Deletion analysis in amphibian oocytes (lampbrush chromosomes), in vitro RNA-binding assays |
Nucleus |
High |
21327109
|
| 2011 |
RBMX (hnRNP G) forms a complex with SRp75 and interacts with hnRNPE2; hnRNP G and SRp75 inhibit splicing of tau exon 10 while hnRNPE2 activates it; SRp75 binds to the proximal downstream intron of tau exon 10 at the FTDP-17 hotspot region. |
Co-transfection, co-immunoprecipitation, RNAi |
Gene |
Medium |
21723381
|
| 2012 |
RBMX accumulates at DNA double-strand break lesions through multiple domains in a PARP1-dependent manner and promotes homologous recombination by facilitating proper BRCA2 expression; identified in a genome-wide siRNA screen as a positive regulator of HR. |
Genome-wide siRNA screen, localization to DNA lesions, PARP1 inhibitor experiments, BRCA2 expression analysis |
Nature cell biology |
High |
22344029
|
| 2012 |
RBMX associates with chromatin and with cohesin subunits Scc1 and Smc3 and cohesion regulator Wapl; RBMX depletion causes premature loss of cohesin from centromeric regions before anaphase, resulting in premature chromatid separation with delocalization of shugoshin complex and outer kinetochore proteins; RBMX maintains cohesion only in the presence of Wapl, suggesting it acts as a Wapl inhibitor; cohesion defects are detectable in G2 phase. |
RNAi, co-immunoprecipitation with cohesin subunits, chromosome spreading, localization studies |
Cell reports |
High |
22832223
|
| 2014 |
The RRM domain of RBMX (hnRNP G) specifically recognizes a 5'-AAN-3' motif (two consecutive adenines); the RRM interacts with SMN2 exon 7 at a polyA tract upstream of the Tra2-β1 binding site; this interaction is required for hnRNP G splicing activity; hnRNP G participates in a trimeric Tra2-β1/hnRNP G/SRSF9 complex on SMN2 exon 7. |
NMR structure of RRM bound to SMN2-derived RNA, mutagenesis of RRM and RNA binding sites, in vitro and in vivo splicing assays |
Nucleic acids research |
High |
24692659
|
| 2015 |
RBMX interacts with Borna disease virus (BDV) nucleoprotein; knockdown of RBMX disrupts viral speckle of transcripts (vSPOTs) formation and reduces BDV transcription and replication. |
Co-immunoprecipitation, siRNA knockdown, immunofluorescence of viral factories |
The Journal of general virology |
Medium |
26333388
|
| 2018 |
RBMX associates with satellite I noncoding RNA specifically during M phase and is a component of the centromeric ncRNP complex; RBMX knockdown induces premature separation of sister chromatid cohesion and abnormal nuclear division; satellite I RNA knockdown reduces RBMX and Sororin levels, suggesting satellite I RNA stabilizes RBMX/Sororin in the ncRNP complex. |
LC/MS of purified satellite I ncRNP complex, siRNA knockdown, immunofluorescence, cell fractionation |
Genes to cells |
Medium |
29383807
|
| 2018 |
RBMX (hnRNP G) prevents inclusion of the central exon between HPV16 splice sites SA3358 and SD3632 on late L1 mRNAs by binding an 8-nucleotide splicing enhancer element, acting as a splicing inhibitor for this viral exon. |
RNA-binding assays, mini-gene splicing assays, mutagenesis of splicing enhancer |
The Journal of general virology |
Medium |
29458523
|
| 2019 |
NORAD lncRNA interaction with RBMX is dispensable for genomic stability maintenance; extensive RNA FISH and fractionation established NORAD localizes predominantly to the cytoplasm; genetic rescue experiments showed PUM binding (not RBMX binding) is required for NORAD-mediated genome maintenance. |
RNA FISH, subcellular fractionation, genetic rescue experiments with NORAD mutants |
eLife |
High |
31343408
|
| 2020 |
RBMX is an ssDNA-binding protein that activates ATR on repetitive DNAs during replication stress; using super-resolution STORM, RBMX and RPA bind adjacent but non-overlapping sites on ssDNA; RBMX facilitates positioning of TopBP1 to activate ATR associated with RPA; this pathway is independent of ssDNA-dsDNA junctions and the 9-1-1 complex; RBMX/RPA are enriched on repetitive DNAs (fragile sites) by ChIP-seq; RBMX depletion causes defective TopBP1 localization, replication defects, micronuclei, and increased sister-chromatid exchange. |
Super-resolution STORM microscopy, ChIP-seq, siRNA knockdown, micronuclei assay, sister chromatid exchange assay |
Cell death and differentiation |
High |
32494026
|
| 2021 |
RBMX interacts with hnRNP A1 via its RGG motif; RBMX competitively inhibits the combination of the hnRNP A1 RGG motif with sequences flanking PKM exon 9, shifting PKM splicing from PKM2 to PKM1, thereby suppressing aerobic glycolysis and bladder cancer tumorigenicity. |
Co-immunoprecipitation, RIP, mini-gene splicing assays, in vitro and in vivo tumor models |
Oncogene |
High |
33564070
|
| 2021 |
RBMX and its retrogene RBMXL1 directly bind mRNAs, control nascent transcription of the CBX5 (HP1α) locus, regulate chromatin accessibility, and are required for myeloid leukemia cell survival; forced CBX5 expression rescues RBMX/L1 depletion-induced growth arrest and apoptosis. |
RIP, ATAC-seq, nascent transcription assays, rescue experiments, loss-of-function in murine and human AML models |
Nature cancer |
High |
34458856
|
| 2021 |
The RBMX RGG/RG motif is methylated by PRMT5; this methylation regulates assembly of RBMX with SRSF1 into higher-order complexes; RBMX/SRSF1 complex binding to MDM4 pre-mRNA promotes exon 6 inclusion and maintains MDM4 protein levels; depletion of RBMX or disruption by PRMT5 inhibition reduces SRSF1 binding to MDM4 pre-mRNA, causes exon 6 skipping, lowers MDM4 protein, and activates p53; Shashi-XLID iPSCs with deleted RGG/RG motif show dysregulated MDM4 splicing, aberrant p53 upregulation, and neural progenitor differentiation/apoptosis defects. |
PRMT5 methylation assay, Co-IP, RIP, mini-gene splicing assays, CRISPR-Cas9 Shashi-XLID iPSC model, transcriptomic analysis |
Cell reports |
High |
34260915
|
| 2022 |
RBMX (hnRNP G) promotes HPV16 E2 mRNA splicing through binding a uridine-less splicing enhancer (ACGAGGACGAGGACAAGGA) upstream of SA2709; the splicing-enhancing function maps to amino acids 236-286 of hnRNP G which also interact with splicing factor U2AF65; DNA damage response (DDR) reduces sumoylation of hnRNP G, enhancing its interaction with E2 mRNAs and U2AF65; hnRNP G also promotes intron retention in HPV16 E6 coding region, inhibiting production of spliced E7 oncogene mRNAs. |
RNA-binding assays, mini-gene splicing assays, mutagenesis, Co-IP with U2AF65, sumoylation assays, DDR induction |
Nucleic acids research |
High |
35357488
|
| 2023 |
RBMX binds TERRA (telomere repeat-containing RNA) and simultaneously binds nuclear exosome targeting protein ZCCHC8; RBMX depletion elevates TERRA levels, enhances telomere R-loop formation, replication stress, and telomere instability; RBMX promotes TERRA degradation by facilitating its transport to the nuclear exosome. |
RIP, Co-IP, R-loop assay, telomere instability assays, siRNA knockdown |
PLoS genetics |
High |
37756323
|
| 2023 |
A Pro162 deletion in RBMX (Gustavson syndrome) leads to disturbed RNA polymerase II transcription (enriched for transcription factors) in neuronal cells; fluorescence polarization assay and prediction tools identify a novel SH3-binding motif in hnRNP G, and the deletion reduces affinity to SH3 domains. |
Genomic sequencing, gene expression analysis in SH-SY5Y neuronal cells, fluorescence polarization binding assay |
European journal of human genetics |
Medium |
37277488
|
| 2024 |
RBMX is dephosphorylated at serine 189 (S189) by mycobacterial phosphatase PstP during Mtb infection; this dephosphorylation alters RBMX splicing activity, causing alternative splicing of PLA2G7 with increased inclusion of exon 9, producing a PLA2G7 isoform that potentiates inflammatory responses. |
Multi-omics (proteomics, phosphoproteomics, interactomics), identification of PstP as the phosphatase, splicing analysis of PLA2G7 |
iMetaOmics |
Medium |
41675711
|
| 2024 |
SOCS5 interacts with RBMX via its SH2 domain (critical residues Y413 and D443 binding to the RBMX RRM domain); SOCS5-RBMX complex co-stimulates the SREBP1 promoter to induce de novo lipogenesis; mutations in the SH2 domain reverse this effect. |
Co-IP, GST-pulldown, promoter reporter assay, mutagenesis of SH2 domain |
NPJ precision oncology |
Medium |
38429411
|
| 2024 |
SUMOylation of RBMX regulates its exosomal miRNA sorting function; deSUMOylated RBMX in diabetic kidney disease promotes packaging of protective miRNAs (miR-26a, miR-23c, miR-874) into exosomes, which target CERS6 to regulate mitochondrial health. |
Co-immunoprecipitation, SUMOylation assays, RNA immunoprecipitation, confocal microscopy, exosome isolation |
Journal of advanced research |
Medium |
39341454
|
| 2005 |
RBMX is required for normal embryonic brain development in zebrafish; rbmx morpholino knockdown causes underdeveloped head and eyes, reduced body size, defective somite patterning, absence of jaws, and severely reduced expression of fore- and hindbrain markers otx2 and krox20. |
Antisense morpholino knockdown in zebrafish, in situ hybridization for neural markers |
Developmental dynamics |
High |
15895365
|
| 2006 |
RBMX functions as a hepatic transcriptional regulator of the SREBP-1c gene in response to high-fructose diet; identified by MALDI-TOF mass spectrometry as the nuclear protein binding to the SRE in the SREBP-1c promoter; anti-RBMX antibody displaces promoter-binding complexes in EMSA; RBMX overexpression or knockdown regulates SREBP-1c promoter activity in hepatoma cells. |
MALDI-TOF MS identification, EMSA with antibody supershift, overexpression and RNAi in hepatoma cells |
FEBS letters |
Medium |
17188681
|
| 2020 |
RBMX specifically binds and stabilizes the lncRNA BLACAT1 mRNA; RIP, RNA pull-down, and RNA stability assays confirmed this interaction; RBMX-mediated BLACAT1 stabilization promotes autophagy, cancer cell stemness, and sorafenib resistance in hepatocellular carcinoma. |
RIP, RNA pull-down, RNA stability assay (actinomycin D chase) |
American journal of cancer research |
Medium |
33294259
|