Affinage

U2SURP

U2 snRNP-associated SURP motif-containing protein · UniProt O15042

Length
1029 aa
Mass
118.3 kDa
Annotated
2026-06-10
25 papers in source corpus 8 papers cited in narrative 8 extracted findings
Cross-family judge faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

U2SURP is a serine/arginine-rich spliceosomal protein that regulates alternative splicing of specific pre-mRNA targets as part of a stable multiprotein complex (PMID:34544891). It forms a tight physical complex with SPF45 and CHERP, and interacts with RBM17/SR-related factors; within this assembly the partners reciprocally stabilize each other's protein levels, and the complex represses inclusion of short exons flanked by suboptimal 3′ splice sites (PMID:30332651, PMID:34544891). Through this activity U2SURP controls splicing of cell-cycle regulators including FOXM1 and SPDL1, such that depletion of any complex member produces G2/M arrest and apoptosis (PMID:34544891), and it regulates an alternative exon in the RNA surveillance factor UPF3A to support proliferation (PMID:30977118). Beyond canonical splicing, U2SURP modulates transcript abundance: it promotes intron-3 removal in SAT1 to stabilize SAT1 mRNA in a MYC–eIF3D-enhanced translational axis (PMID:36907504), is recruited by the lncRNA HNF1A-AS1 via its RRM-dependent domain to drive a CD44 isoform switch promoting invasion (PMID:40518456), and stabilizes CREB3L2 mRNA to activate RIOK1 and confer drug resistance (PMID:41997041). Across these settings U2SURP behaves as a pro-proliferative, pro-metastatic factor upregulated in multiple cancers (PMID:30977118, PMID:36907504, PMID:40518456).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 2018 High

    Established that U2SURP is not an isolated factor but part of a co-regulated spliceosomal module, answering whether it has stable physical partners.

    Evidence Co-IP plus knockdown and RNA-seq in mouse and human cells

    PMID:30332651

    Open questions at the time
    • Did not define the splice-site features targeted
    • Functional consequences described only at the transcriptome level, not phenotype
  2. 2019 High

    Showed the U2SURP–CHERP complex regulates a defined target (UPF3A exon 4) with proliferative consequences, linking the complex to cancer cell growth.

    Evidence Co-IP, RNA immunoprecipitation, splicing analysis, and xenograft rescue experiments

    PMID:30977118

    Open questions at the time
    • Mechanism of exon selection not resolved
    • Restricted to colorectal cancer context
  3. 2021 High

    Defined the biochemical logic of the complex—repression of short exons with weak 3′ splice sites—and tied it causally to G2/M control via FOXM1 and SPDL1.

    Evidence Co-IP, minigene splicing assays, cell-cycle analysis, and splicing-mimicking epistasis in HeLa cells

    PMID:34544891

    Open questions at the time
    • No structural model of the SPF45/CHERP/U2SURP complex
    • Rescue was only partial, implying additional targets
  4. 2023 Medium

    Placed U2SURP in a signaling axis by showing MYC drives its translation via eIF3D and that it acts upstream of SAT1 through intron retention/removal affecting mRNA stability.

    Evidence Translation and mRNA-stability assays, RT-PCR splicing analysis, and xenograft rescue in TNBC cells

    PMID:36907504

    Open questions at the time
    • No reconstitution of the splicing event
    • Direct binding to SAT1 pre-mRNA not demonstrated
  5. 2025 Medium

    Demonstrated lncRNA-directed recruitment of U2SURP, showing HNF1A-AS1 engages its RRM domain to redirect CD44 splicing toward a pro-metastatic isoform.

    Evidence RNA pull-down, Co-IP, FISH, domain-deletion, and rescue assays in pancreatic cancer cells

    PMID:40518456

    Open questions at the time
    • Single-lab study
    • Generality of lncRNA-guided targeting to other transcripts unknown
  6. 2026 Medium

    Extended U2SURP function to mRNA stabilization of CREB3L2 with downstream RIOK1 activation and drug-resistance phenotypes.

    Evidence mRNA stability assays, knockdown/overexpression rescue, and xenograft models in HCC cells

    PMID:41997041

    Open questions at the time
    • Mechanism of mRNA stabilization undefined
    • Direct U2SURP–CREB3L2 interaction not shown
  7. 2025 Low

    Associated U2SURP with Ras/MAPK output via reduced p-ERK after knockdown.

    Evidence siRNA knockdown and p-ERK Western blot in CML cells

    PMID:41274252

    Open questions at the time
    • Single downstream readout with no direct mechanistic link to ERK
    • Not confirmed independently
  8. 2024 Low

    Nominated U2SURP as a DNA damage response factor through proximity to γH2AX-marked chromatin.

    Evidence TurboID proximity proteomics with γH2AX-binding BRCT probes (preprint)

    PMID:bio_10.1101_2024.10.23.619792

    Open questions at the time
    • Preprint, not peer-reviewed
    • Mechanistic role in DNA repair undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How U2SURP selects its specific exon and mRNA targets across diverse contexts—and whether its splicing activity and reported mRNA-stabilization/DDR roles are mechanistically distinct functions—remains unresolved.
  • No structural model of the complex or RNA recognition
  • Unclear how splicing repression relates to mRNA stabilization
  • DDR role uncharacterized at the mechanistic level

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 3
Partners
CHERPRBM17SPF45
Complex memberships
SNAI2-HNF1A-AS1-U2SURP complexSPF45-CHERP-U2SURP splicing complex

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 U2SURP physically interacts with RBM17 and CHERP as part of a spliceosomal complex; the three proteins reciprocally regulate each other's stability in both mouse and human cells. Individual knockdown of each protein induces overlapping changes in splicing and gene expression of transcripts enriched for RNA-processing factors. Co-immunoprecipitation, knockdown experiments, RNA-seq in mouse and human cells Cell reports High 30332651
2021 U2SURP (SR140), SPF45, and CHERP form a tight physical complex that regulates alternative splicing by repressing short exons flanked by suboptimal 3′ splice sites. Target alternative exons are embedded in cell-cycle genes including FOXM1 (G2/M regulator) and SPDL1 (spindle regulator). Knockdown of any of the three factors causes G2/M arrest and enhanced apoptosis in HeLa cells; promoting the FOXM1 or SPDL1 splicing changes induced by knockdown partially recapitulates effects on cell growth. Co-immunoprecipitation, siRNA knockdown, RNA-seq, minigene splicing assays, cell-cycle analysis, epistasis via splicing-mimicking constructs RNA (New York, N.Y.) High 34544891
2019 U2SURP (SR140) and CHERP form a protein complex that stabilizes each other; both are upregulated in colorectal cancer. The complex regulates alternative splicing of UPF3A (binding specifically to its regulated exon 4), and UPF3A knockdown recapitulates proliferation defects caused by CHERP/SR140 depletion both in vitro and in mice. Co-immunoprecipitation, siRNA knockdown, alternative splicing analysis, RNA immunoprecipitation, xenograft mouse model, rescue experiments International journal of cancer High 30977118
2023 MYC enhances U2SURP translation through an eIF3D (eukaryotic translation initiation factor 3 subunit D)-dependent mechanism. U2SURP promotes alternative splicing of SAT1 pre-mRNA by removal of intron 3, increasing SAT1 mRNA stability and protein expression. Re-expression of SAT1 in U2SURP-depleted TNBC cells partially rescues impaired malignant phenotypes both in vitro and in vivo, placing U2SURP downstream of MYC and upstream of SAT1 in a defined signaling axis. Knockdown/overexpression assays, splicing analysis (RT-PCR), mRNA stability assays, xenograft mouse model, rescue experiments, ribosome-related translation assays Cancer letters Medium 36907504
2025 HNF1A-AS1 lncRNA recruits U2SURP through its RRM-dependent domain via the 1001–1500 nt region (BR3) to form a functional SNAI2-HNF1A-AS1-U2SURP complex in the nucleus of pancreatic cancer cells. This complex specifically promotes alternative splicing of CD44 pre-mRNA, converting it from the standard isoform to CD44v(3-10), thereby promoting invasion and metastasis. RNA pull-down assay, Co-IP, FISH, mRNA sequencing, rescue assays, domain deletion experiments Journal of gastroenterology Medium 40518456
2026 U2SURP increases CREB3L2 mRNA stability, leading to transcriptional activation of RIOK1 and reduced sensitivity to lenvatinib in hepatocellular carcinoma cells. Knockdown of CREB3L2 attenuates the U2SURP-mediated drug resistance phenotype in vitro and in xenograft models. mRNA stability assays, overexpression/knockdown, rescue experiments, xenograft mouse model Pathology, research and practice Medium 41997041
2025 U2SURP knockdown suppresses the expression of p-ERK, implicating U2SURP in the Ras/MAPK signaling pathway in CML cells. This effect was identified in the context of the circ_0058493/miR-548b-3p/U2SURP regulatory axis. siRNA knockdown, Western blotting for p-ERK Biochemical and biophysical research communications Low 41274252
2024 U2SURP was identified as a novel effector of the DNA damage response using proximity ligation (TurboID) tethered via a γH2AX-binding BRCT domain probe; functional characterization confirmed U2SURP as a previously uncharacterized DNA damage response factor. Proximity ligation/TurboID proteomics, engineered γH2AX-binding BRCT probes in living cells, functional characterization of hits bioRxivpreprint Low bio_10.1101_2024.10.23.619792

Source papers

Stage 0 corpus · 25 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Neural mechanisms underlying migrating motor complex formation in mouse isolated colon. British journal of pharmacology 63 11159701
1998 Steric hindrance mutagenesis versus alanine scan in mapping of ligand binding sites in the tachykinin NK1 receptor. Molecular pharmacology 61 9443945
2018 RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins. Cell reports 53 30332651
2001 Combinations of neurokinin receptor antagonists reduce visceral hyperalgesia. The Journal of pharmacology and experimental therapeutics 44 11561069
1998 Effect of tachykinin receptor antagonists in experimental neuropathic pain. European journal of pharmacology 41 9865506
2020 Identification of spliceosome components pivotal to breast cancer survival. RNA biology 32 32965163
2023 MYC-driven U2SURP regulates alternative splicing of SAT1 to promote triple-negative breast cancer progression. Cancer letters 26 36907504
2020 The plasma peptides of sepsis. Clinical proteomics 26 32636717
1998 Point mutation increases a form of the NK1 receptor with high affinity for neurokinin A and B and septide. British journal of pharmacology 26 9786514
2021 Alternative splicing regulation of cell-cycle genes by SPF45/SR140/CHERP complex controls cell proliferation. RNA (New York, N.Y.) 24 34544891
2019 U2-related proteins CHERP and SR140 contribute to colorectal tumorigenesis via alternative splicing regulation. International journal of cancer 21 30977118
2002 Novel method for the study of receptor Ca2+ signalling exemplified by the NK1 receptor. Journal of receptor and signal transduction research 12 12503619
2016 Identification and validation of Aeluropus littoralis reference genes for Quantitative Real-Time PCR Normalization. Journal of biological research (Thessalonike, Greece) 10 27437194
2006 Neurokinin 1 receptor signaling mediates sex differences in mu and kappa opioid-induced enhancement of contact hypersensitivity. Journal of neuroimmunology 9 17023055
1997 Neurokinin A-induced vasoconstriction and muscular contraction in the rat isolated stomach: mediation by distinct and unusual neurokinin2 receptors. The Journal of pharmacology and experimental therapeutics 7 9190865
2019 VEGF-A-Cleavage by FSAP and Inhibition of Neo-Vascularization. Cells 6 31698750
2024 Alternative Splicing Reveals Acute Stress Response of Litopenaeus vannamei at High Alkalinity. Marine biotechnology (New York, N.Y.) 4 38206418
1996 Structural motifs encoded by individual exons of the human neurokinin-1 receptor gene interact differentially with selective agonists and antagonists. Journal of neurochemistry 3 8752126
2006 Role of the tachykinin NK(1) receptor in mediating contraction to 5-hydroxytryptamine and antigen in the mouse trachea. Pulmonary pharmacology & therapeutics 2 16919985
2025 Exosomal circ_0058493 promotes imatinib resistance via miR-548b-3p/U2SURP axis in CML cells. Biochemical and biophysical research communications 1 41274252
2020 Use of bioinformatic analyses in identifying characteristic genes and mechanisms active in the progression of idiopathic thrombocytopenic purpura in individuals with different phenotypes. The Journal of international medical research 1 33222560
2026 U2SURP increases CREB3L2 RNA stability and RIOK1 transcription to enhance lenvatinib resistance in hepatocellular carcinoma cells. Pathology, research and practice 0 41997041
2025 Identification of cancer cell-intrinsic biomarkers associated with tumor progression and characterization of SFTA3 as a tumor suppressor in lung adenocarcinomas. BMC cancer 0 39780110
2025 Comprehensive systems biology analysis reveals splicing factor contributions to cutaneous melanoma progression. Scientific reports 0 40108329
2025 aGenome-scale activation screen reveals lncRNA HNF1A-AS1 promotes pancreatic cancer metastasis through interacting with U2SURP to increase CD44 alternative splicing. Journal of gastroenterology 0 40518456

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