Affinage

RBM7

RNA-binding protein 7 · UniProt Q9Y580

Length
266 aa
Mass
30.5 kDa
Annotated
2026-06-10
13 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM7 is an RNA-recognition motif (RRM)-containing subunit of the nuclear exosome targeting (NEXT) complex that recognizes U-rich pyrimidine and AU-rich RNA sequences and directs non-coding and structured RNAs toward the nuclear exosome for surveillance and degradation (PMID:25852104). Its RRM both binds RNA—through two critical phenylalanine residues—and tethers RBM7 into NEXT by docking onto a proline-rich segment of ZCCHC8, with the same surface able to engage a structurally similar segment of the splicing factor SAP145, linking exosome targeting to the spliceosome (PMID:25852104, PMID:27905398). Through this activity RBM7/NEXT carries out snRNA 3'-end surveillance and degradation of PROMPTs (PMID:25852104, PMID:25525152). RBM7's RNA-binding output is gated by stress signaling: p38MAPK/MK2 phosphorylates RBM7 at S136, reducing RNA association and consequently stabilizing PROMPTs without altering their transcription (PMID:25525152); under genotoxic stress p38MAPK activation additionally redirects RBM7 to the 7SK snRNP, where it displaces and activates P-TEFb to promote RNA Pol II pause release and a pro-survival DNA-damage transcriptional program (PMID:30824372). Beyond non-coding RNA turnover, RBM7 shapes specific protein-coding outputs—stabilizing CDK1 mRNA via 3'-UTR AU-rich elements to drive cell-cycle progression (PMID:33145401), destabilizing FBXL16 mRNA to suppress ferroptosis (PMID:41381783), and controlling MFGE8 alternative splicing to restrain migration and invasion (PMID:38995840)—thereby influencing proliferation, cancer metastasis, and chemoresistance. A homozygous loss-of-function RBM7 mutation underlies an SMA-like motor neuropathy, with patient and zebrafish phenotypes placing RBM7 in the same essential RNA-processing pathway as exosome core subunits (PMID:27193168).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2014 High

    Established that RBM7's central RNA-binding activity is a regulated node, by showing that stress-activated p38MAPK/MK2 phosphorylates RBM7 at S136 to switch off exosome targeting of non-coding RNAs.

    Evidence In vitro kinase assay, S136 phospho-site mapping, S136A mutant RNA-binding assays, and PROMPT stability measurements

    PMID:25525152

    Open questions at the time
    • Does not resolve how phosphorylation structurally disrupts the RRM-RNA interface
    • Scope of the phospho-regulated noncoding transcriptome beyond tested PROMPTs not defined
  2. 2015 High

    Defined the molecular basis of RBM7 RNA recognition, showing the RRM binds U-rich pyrimidine sequences via two phenylalanines and that this activity underlies NEXT-mediated snRNA surveillance.

    Evidence Crystal structure of RBM7 RRM, phenylalanine mutagenesis, RNA-binding assays, RIP, and depletion with RNA-seq

    PMID:25852104

    Open questions at the time
    • Structure of RRM bound to RNA not solved
    • Full set of physiological RNA targets of NEXT not enumerated
  3. 2016 High

    Showed how RBM7 is physically incorporated into NEXT and revealed a potential exosome-spliceosome link, by mapping the RRM to a proline-rich segment of ZCCHC8 and a similar segment of SAP145.

    Evidence 2.0 Å crystal structure of RBM7 RRM–ZCCHC8 complex with biochemical binding assays and structural comparison

    PMID:27905398

    Open questions at the time
    • Functional consequence of the RBM7-SAP145 interaction in vivo not established
    • Whether RNA binding and ZCCHC8 binding are mutually exclusive not resolved
  4. 2016 Medium

    Provided an additional structural view of the isolated RBM7 RRM, but without functional consequence beyond the existing model.

    Evidence X-ray crystallography at 2.5 Å with molecular replacement

    PMID:27139832

    Open questions at the time
    • Pentameric assembly attributed to crystal packing, not biologically validated
    • No functional validation accompanying the structure
  5. 2016 Medium

    Connected RBM7 to human disease and confirmed its essential role in RNA processing, by linking a homozygous loss-of-function mutation to motor neuropathy and recapitulating neuronal defects in zebrafish overlapping exosome-subunit phenotypes.

    Evidence Patient fibroblast RNA-seq, zebrafish morpholino knockdown with neuronal phenotype, and epistasis with exosc8/exosc3

    PMID:27193168

    Open questions at the time
    • Disease mechanism inferred from pathway overlap rather than direct biochemical dissection
    • Single patient; allelic spectrum not defined
  6. 2019 High

    Revealed a moonlighting function distinct from RNA degradation, showing that genotoxic stress redirects RBM7 to the 7SK snRNP to release and activate P-TEFb, driving Pol II pause release and a pro-survival response.

    Evidence Reciprocal Co-IP with 7SK snRNP, chromatin fractionation of P-TEFb, Pol II ChIP, 4sU-seq, and loss-of-function apoptosis readout

    PMID:30824372

    Open questions at the time
    • How phosphorylation state of RBM7 coordinates NEXT versus 7SK engagement not resolved
    • Direct binding partner within 7SK snRNP for RBM7 not pinpointed structurally
  7. 2020 Medium

    Extended RBM7 function to subnuclear body homeostasis, showing it binds NEAT1 and that elevated RBM7 degrades NEAT1 speckles, disperses BRCA1, and drives apoptosis with downstream pro-fibrotic signaling.

    Evidence Rbm7 conditional knockout mouse bleomycin model, RIP for NEAT1, BRCA1 immunofluorescence, apoptosis assays, and CXCL12 measurement

    PMID:32187520

    Open questions at the time
    • NEAT1→BRCA1 dispersion→apoptosis chain rests partly on correlative evidence
    • Direct degradation of NEAT1 by RBM7-NEXT not biochemically reconstituted
  8. 2020 Medium

    Established a stabilizing, mRNA-specific role for RBM7, showing direct binding to AU-rich elements in CDK1 mRNA lengthens its half-life to drive cell-cycle progression and proliferation.

    Evidence RIP, actinomycin D mRNA half-life assay, CDK1 rescue with ARE-mutant control, and xenograft proliferation assays

    PMID:33145401

    Open questions at the time
    • Mechanism of stabilization versus its known destabilizing/degradative roles not reconciled
    • No in vitro reconstitution of CDK1 mRNA stabilization
  9. 2024 Medium

    Identified a splicing-regulatory function, showing RBM7 promotes MFGE8 exon-7 inclusion to favor a migration-inhibitory isoform and negatively regulates NF-κB signaling.

    Evidence RBM7 knockdown/overexpression, RT-PCR splicing assays, STAT1 phospho Western blot, HUVEC tube formation, and lung metastasis mouse model

    PMID:38995840

    Open questions at the time
    • Mechanism by which RBM7 directs splice-site selection not biochemically reconstituted
    • Direct binding of RBM7 to MFGE8 pre-mRNA not mapped
  10. 2025 Medium

    Demonstrated an mRNA-destabilizing role with metabolic consequences, showing RBM7 binds and destabilizes FBXL16 mRNA to suppress mitochondrial dysfunction and ferroptosis in chemoresistant glioblastoma.

    Evidence Co-IP, RIP, actinomycin D mRNA stability assay, FBXL16 knockdown rescue with ferroptosis readouts, and xenograft model

    PMID:41381783

    Open questions at the time
    • Destabilization mechanism not reconstituted in vitro
    • Whether NEXT/exosome mediates FBXL16 mRNA decay not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBM7 partitions between its NEXT/exosome degradative role, its 7SK/P-TEFb transcriptional role, and its sequence-specific mRNA stabilization/destabilization and splicing activities—and how phosphorylation orchestrates these switches—remains unresolved.
  • No unified model reconciling opposing stabilizing and destabilizing mRNA effects
  • Determinants of target selection across these distinct activities unknown
  • Structural basis for stress-dependent reassignment of RBM7 from NEXT to 7SK not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
P-TEFBSAP145ZCCHC8
Complex memberships
7SK snRNPNEXT complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 The RRM domain of RBM7 mediates U-rich pyrimidine RNA sequence binding within the NEXT complex; two critical phenylalanine residues in the RRM are required for RNA interaction and for NEXT complex association with snRNAs in vivo. RBM7/NEXT depletion causes accumulation of mature and 3'-end extended forms of snRNAs, implicating NEXT in snRNA surveillance/snRNP biogenesis. Crystal structure of RBM7 RRM; site-directed mutagenesis of phenylalanine residues; RNA-binding assays; RIP; depletion experiments with RNA-seq readout Nucleic acids research High 25852104
2016 A proline-rich segment of ZCCHC8 is the direct interaction site for the RRM of RBM7, incorporating RBM7 into the NEXT complex. The same RRM of RBM7 can also bind a structurally similar proline-rich segment of the splicing factor SAP145, suggesting dual interactions linking the exosome to the spliceosome. Crystal structure of RBM7 RRM–ZCCHC8 proline-rich segment complex at 2.0 Å; biochemical binding assays; sequence/structural comparison with SAP145 Nature communications High 27905398
2014 RBM7 is phosphorylated by the p38MAPK/MK2 axis at serine 136 (S136). This phosphorylation strongly decreases RBM7's RNA-binding capacity. Inhibition of p38MAPK or the S136A mutation increases RBM7–RNA association. Phosphorylation of RBM7 during stress increases stability of PROMPTs (e.g., proRBM39, proEXT1, proDNAJB4) without changing their transcription rate, indicating that p38MAPK/MK2 modulates the noncoding transcriptome by blocking RBM7-mediated exosome targeting. In vitro kinase assay; phospho-site mapping (S136); RNA-binding assays with RBM7-S136A mutant; RNAPII ChIP; PROMPT stability measurements; overexpression of phospho-mutant RNA (New York, N.Y.) High 25525152
2019 Following genotoxic stress, p38MAPK activation triggers enhanced binding of RBM7 to core subunits of the 7SK snRNP, releasing P-TEFb from the inhibitory 7SK snRNP complex. Released P-TEFb relocates to chromatin to promote RNA Pol II pause release, driving transcription of short DDR genes and non-coding RNAs. Disruption of the RBM7–P-TEFb axis causes hypersensitivity to DNA-damaging agents via apoptosis. Co-immunoprecipitation of RBM7 with 7SK snRNP components; chromatin fractionation of P-TEFb; RNA Pol II ChIP; 4sU-seq; loss-of-function with apoptosis readout; genotoxic stress treatments Molecular cell High 30824372
2016 Crystal structure of the isolated RRM domain of human RBM7 was determined at 2.5 Å resolution, revealing a ring-shaped pentameric assembly (attributed to crystal packing). The structure required molecular replacement using RBM8 and CBP20 RRM structures as search models. X-ray crystallography at 2.5 Å; molecular replacement Acta crystallographica. Section F, Structural biology communications Medium 27139832
2020 RBM7 binds noncoding RNAs that form subnuclear bodies including NEAT1 speckles. Dysregulated (elevated) RBM7 expression leads to nuclear degradation of NEAT1 speckles, dispersion of the DNA repair protein BRCA1, and triggering of apoptosis in lung epithelial cells, which then produce CXCL12 to recruit pro-fibrotic SatMs. Rbm7 conditional knockout mouse (bleomycin fibrosis model); RNA immunoprecipitation for NEAT1 binding; immunofluorescence for BRCA1 dispersion; apoptosis assays; CXCL12 measurement Immunity Medium 32187520
2020 RBM7 directly binds AU-rich elements (AREs) in the 3'-UTR of CDK1 mRNA, stabilizing it and lengthening its half-life. This stabilization promotes breast cancer cell proliferation and G1-S progression; CDK1 overexpression rescues the proliferative defect caused by RBM7 knockdown, whereas a mutant CDK1 unable to bind AREs does not. RIP assay; mRNA half-life assay (actinomycin D); RBM7 knockdown/overexpression with CDK1 rescue; in vitro and in vivo (xenograft) proliferation assays NPJ breast cancer Medium 33145401
2024 RBM7 controls the alternative splicing of MFGE8, promoting inclusion of exon 7 to produce the long isoform MFGE8-L over the truncated isoform MFGE8-S. MFGE8-L attenuates STAT1 phosphorylation and alters cell adhesion molecules to inhibit breast cancer migration and invasion, whereas MFGE8-S (lacking the second F5/8 type C domain) has the opposite effect. RBM7 also negatively regulates the NF-κB cascade; RBM7 silencing enhances HUVEC tube formation that is blocked by an NF-κB inhibitor. RBM7 knockdown/overexpression; RT-PCR splicing assays; lung metastasis mouse model; STAT1 phosphorylation Western blot; NF-κB pathway analysis; HUVEC tube formation assay eLife Medium 38995840
2025 RBM7 directly interacts with FBXL16 mRNA and destabilizes it, reducing FBXL16 protein levels. This suppresses mitochondrial dysfunction and ferroptosis in TMZ-resistant glioblastoma cells. FBXL16 knockdown reverses ferroptosis and chemosensitivity induced by RBM7 loss, placing RBM7 upstream of FBXL16 in a resistance pathway. Co-immunoprecipitation; RNA immunoprecipitation; actinomycin D mRNA stability assay; RBM7 knockdown with ferroptosis/mitochondrial readouts; xenograft model Molecular genetics and genomics : MGG Medium 41381783
2016 A homozygous loss-of-function mutation in RBM7 in a patient with SMA-like motor neuropathy causes altered RNA metabolism in primary fibroblasts. Knockdown of rbm7 in zebrafish produces motor neuron and cerebellar defects, overlapping with those seen for exosc8/exosc3 knockdown, placing RBM7 in the same essential RNA-processing pathway required for neuronal differentiation. Patient fibroblast RNA-seq; zebrafish rbm7 morpholino knockdown with motor neuron/cerebellar phenotype readout; genetic epistasis comparison with exosc8/exosc3 Human molecular genetics Medium 27193168

Source papers

Stage 0 corpus · 13 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress. Molecular cell 72 30824372
2015 RBM7 subunit of the NEXT complex binds U-rich sequences and targets 3'-end extended forms of snRNAs. Nucleic acids research 58 25852104
2016 Structure of the RBM7-ZCCHC8 core of the NEXT complex reveals connections to splicing factors. Nature communications 43 27905398
2016 Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy. Human molecular genetics 39 27193168
2020 Dysregulated Expression of the Nuclear Exosome Targeting Complex Component Rbm7 in Nonhematopoietic Cells Licenses the Development of Fibrosis. Immunity 38 32187520
2014 p38MAPK/MK2-mediated phosphorylation of RBM7 regulates the human nuclear exosome targeting complex. RNA (New York, N.Y.) 34 25525152
2020 Oncogenic action of the exosome cofactor RBM7 by stabilization of CDK1 mRNA in breast cancer. NPJ breast cancer 25 33145401
2024 RBM7 deficiency promotes breast cancer metastasis by coordinating MFGE8 splicing switch and NF-kB pathway. eLife 9 38995840
2021 Novel insights into the pathogenesis of lung fibrosis: the RBM7-NEAT1-CXCL12-SatM axis at fibrosis onset. International immunology 5 34165514
2016 RRM domain of human RBM7: purification, crystallization and structure determination. Acta crystallographica. Section F, Structural biology communications 5 27139832
2020 Rbm7 in Structural Cells: A NEAT Way to Control Fibrosis. Immunity 4 32187513
2025 RBM7 suppresses mitochondrial dysfunction and ferroptosis by destabilizing FBXL16 mRNA to enhance Temozolomide resistance in glioblastoma. Molecular genetics and genomics : MGG 0 41381783
2019 Activation of P-TEFb by RBM7: To Live or Let Die. Molecular cell 0 31002802

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