Affinage

CSDE1

Cold shock domain-containing protein E1 · UniProt O75534

Length
798 aa
Mass
88.9 kDa
Annotated
2026-04-28
77 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CSDE1 (UNR) is a cytoplasmic RNA-binding protein containing five cold-shock domains (CSDs) that functions as a master post-transcriptional regulator of mRNA translation, stability, and miRNA biogenesis across diverse cell types. It acts as an RNA chaperone at viral and cellular IRES elements—remodeling RNA structure cooperatively with PTB to expose ribosome landing sites—and stimulates cap-dependent translation by promoting PABP1–eIF4G interactions through CSD2 and CSD4 (PMID:12667457, PMID:26936655). CSDE1 couples translation to mRNA decay via its interaction with PABP and the CCR4 deadenylase, thereby controlling the expression kinetics of target mRNAs including c-fos, Gata6, Bach2, VIM, and Cdk6 in contexts ranging from stem cell self-renewal and neuronal migration to B-cell differentiation and melanoma metastasis (PMID:15314026, PMID:27908735, PMID:40133358, PMID:40555862). CSDE1 additionally participates in miRNA maturation by interacting with AGO2 through CSD1 to promote miR-451 processing and miR-486 passenger-strand cleavage, and in Drosophila it serves as a sex-specific translational corepressor of msl-2 mRNA in a ternary complex with SXL and PABP (PMID:37493604, PMID:41905768, PMID:25209665).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1994 High

    Establishing that UNR is a cytoplasmic single-stranded nucleic acid–binding protein resolved its basic biochemical identity and subcellular context.

    Evidence In vitro binding assays and subcellular fractionation/immunolocalization in mammalian cells

    PMID:7518919

    Open questions at the time
    • Physiological RNA targets unknown
    • No functional role assigned
    • Mechanism of cytoplasmic retention undefined
  2. 1999 High

    Defining UNR's RNA-binding specificity (purine-rich AAGUA/G motif, ~10 nM Kd) and demonstrating that multiple CSDs cooperate for high-affinity binding established the modular logic of its RNA recognition.

    Evidence SELEX with recombinant UNR, domain dissection with truncated CSD constructs

    PMID:10101203

    Open questions at the time
    • Structural basis for multi-CSD cooperativity unknown
    • In vivo target repertoire not mapped
  3. 1999 High

    Identifying UNR as an IRES trans-acting factor (ITAF) that synergizes with PTB to drive HRV IRES-dependent translation, and discovering its partner UNRIP/STRAP, established its first functional role in translational control.

    Evidence RNA-affinity purification from HeLa extracts, co-IP, reconstitution in reticulocyte lysate translation assays

    PMID:10049359

    Open questions at the time
    • Mechanism of synergy with PTB unresolved
    • Role of UNRIP/STRAP in IRES activity unclear
  4. 2003 High

    Demonstrating that UNR acts as an RNA chaperone on the Apaf-1 IRES—prebinding to remodel RNA structure and expose the ribosome landing site for PTB—provided a mechanistic framework for ITAF function beyond simple recruitment.

    Evidence RNA structural probing, binding-site mapping, and functional translation assays with ordered addition of UNR and PTB

    PMID:12610110 PMID:12667457

    Open questions at the time
    • Generalizability of ordered-chaperone model to other cellular IRESes untested
    • No structural model at atomic resolution
  5. 2004 High

    Linking UNR to mRNA decay via the c-fos mCRD showed that UNR couples translation to deadenylation through interactions with PABP and CCR4, establishing a translation-dependent mRNA destabilization mechanism.

    Evidence Co-IP of UNR with PABP and CCR4, functional mRNA decay assays with translation inhibitors

    PMID:15314026

    Open questions at the time
    • Direct enzymatic role versus scaffolding function not distinguished
    • Whether this mechanism generalizes beyond c-fos unclear
  6. 2006 High

    Identification of Drosophila UNR as a corepressor recruited by SXL to silence msl-2 translation revealed a sex-specific translational repression mechanism and expanded UNR's roles beyond IRES activation to include translational inhibition.

    Evidence mRNP purification with MS identification, co-IP, translational repression assays in Drosophila S2 cells

    PMID:16452508 PMID:16452509

    Open questions at the time
    • Human ortholog involvement in analogous repression unknown
    • Mechanism of ribosome exclusion not yet defined
  7. 2009 High

    Reconstituting the SXL-UNR-PABP ternary repression mechanism showed that the complex blocks 43S ribosome recruitment after eIF4F assembly, defining the step at which translational repression occurs.

    Evidence Biochemical assays measuring eIF4F and ribosome recruitment with purified components and poly(A)-dependent translation

    PMID:19941818

    Open questions at the time
    • Structural basis for ribosome exclusion at atomic level unknown
    • Whether PABP interaction is required for all UNR-mediated repression unclear
  8. 2010 High

    Solving NMR structures of all five human CSDs revealed that CSD1 has distinctive RNP motif conformations correlating with its superior RNA-binding affinity, providing a structural rationale for domain-specific functions.

    Evidence Solution NMR of all five isolated CSD domains

    PMID:20213426

    Open questions at the time
    • Full-length protein structure unavailable
    • Inter-domain arrangements and RNA-bound conformations unresolved
  9. 2014 High

    The 2.8 Å crystal structure of the Sxl-Unr CSD1-msl2 RNA ternary complex revealed intertwined protein–RNA contacts and a ~1000-fold cooperative increase in Unr CSD1 RNA affinity, providing the first atomic-resolution view of UNR in a functional complex.

    Evidence X-ray crystallography, NMR, SAXS, and SANS of the ternary complex

    PMID:25209665

    Open questions at the time
    • Structure includes only CSD1; multi-CSD architecture on RNA unknown
    • Applicability to mammalian complexes not demonstrated structurally
  10. 2011 Medium

    Showing that UNR-null ES cells spontaneously differentiate into primitive endoderm due to Gata6 mRNA stabilization established CSDE1 as a gatekeeper of stem cell fate through mRNA destabilization.

    Evidence Unr−/− ES cell analysis, Gata6 mRNA stability assays, rescue by re-expression

    PMID:21954113

    Open questions at the time
    • Whether Gata6 is a direct binding target or indirect effect not fully resolved
    • Signaling pathways upstream of UNR in this context unknown
  11. 2016 High

    Genome-wide iCLIP and ribosome profiling in melanoma revealed a CSDE1-regulated pro-metastatic RNA regulon (including VIM and RAC1), positioning CSDE1 as a post-transcriptional driver of cancer invasion.

    Evidence iCLIP-seq, RNA-seq, ribosome profiling, loss/gain-of-function in melanoma cells and mouse xenografts

    PMID:27908735

    Open questions at the time
    • Regulatory logic distinguishing stabilization versus translational targets unclear
    • Upstream signals activating CSDE1 in melanoma not identified
  12. 2016 High

    Demonstrating that CSD2 and CSD4 stimulate cap-dependent translation and that CSDE1 stabilizes the PABP1–eIF4G interaction showed that CSDE1 functions as a general translation enhancer beyond IRES contexts.

    Evidence In vitro translation with CSD mutants, co-IP of PABP1/eIF4G, siRNA knockdown with polysome analysis

    PMID:26936655

    Open questions at the time
    • Whether this general stimulation is RNA target-selective in vivo unclear
    • Mechanism of CSD2/CSD4 specificity not structurally resolved
  13. 2017 High

    CSDE1 was shown to regulate human embryonic stem cell identity and neurogenesis by binding and controlling FABP7 and VIM mRNA stability/translation, extending its stem cell role to human pluripotency.

    Evidence KO/OE in hESCs, iCLIP, RNA-seq, ribosome profiling

    PMID:29129916

    Open questions at the time
    • How CSDE1 switches between mRNA stabilization and destabilization on different targets unclear
  14. 2019 High

    HITS-CLIP in neurons combined with functional knockdown showed that CSDE1 controls neurite outgrowth, dendritic spine morphology, and synapse formation, with targets enriched for autism-associated and FMRP target genes.

    Evidence HITS-CLIP in mouse cortical neurons, CSDE1 KD with morphological and electrophysiological readouts, cross-validated in Drosophila

    PMID:31579823

    Open questions at the time
    • Direct causal link to autism spectrum disorder in humans not established genetically
    • Which specific target mRNAs mediate synapse phenotype unknown
  15. 2022 High

    CSDE1 was found to enable oncogene-induced senescence by stabilizing SASP factor mRNAs and repressing Ybx1 translation, revealing a context-dependent tumor-suppressor function opposing its pro-metastatic role in melanoma.

    Evidence CSDE1 depletion in primary keratinocytes, transcriptome/translatome profiling, in vivo tumor formation assays

    PMID:35021076

    Open questions at the time
    • How cell type determines whether CSDE1 acts as oncogene or tumor suppressor unresolved
    • Post-translational modifications governing context-specificity not systematically mapped
  16. 2023 Medium

    Demonstrating that CSDE1 promotes AGO2-dependent miR-451 maturation and PARN-mediated trimming expanded its functional repertoire to miRNA biogenesis, with CSD1-dependent AGO2 interaction as the critical determinant.

    Evidence RNA-IP, in vitro AGO2 processing assays, domain-dependency studies, PARN interaction assays in erythroid cells

    PMID:37493604

    Open questions at the time
    • Whether CSDE1 affects biogenesis of miRNAs beyond miR-451 and miR-486 broadly untested
    • Structural basis for CSD1-AGO2 interaction unknown
  17. 2025 High

    The Csde1-Strap complex was shown to couple Bach2 mRNA decay with translation during B-cell differentiation, demonstrating that the translation–decay coupling mechanism originally described for c-fos operates in a physiological cell fate decision.

    Evidence RNA interactome capture-coupled CRISPR screen, co-IP of Csde1-Strap, RIP for Bach2 mRNA, mRNA stability and translation assays in B cells

    PMID:40133358

    Open questions at the time
    • Whether Strap is required for all CSDE1-mediated decay coupling or only specific targets unknown
    • Deadenylase identity in the B-cell context not confirmed
  18. 2025 Medium

    CSDE1 phosphorylation during melanoma transformation correlates with enhanced ribosome association, suggesting post-translational modification as a mechanism switching CSDE1 activity in cancer.

    Evidence 2D gel electrophoresis, phosphorylation site mapping, interactome proteomics, subcellular fractionation comparing melanocytes and melanoma cells

    PMID:40883018

    Open questions at the time
    • Kinase(s) responsible for CSDE1 phosphorylation not identified
    • Causal relationship between phosphorylation and ribosome binding not demonstrated by mutagenesis
  19. 2025 Medium

    CSDE1 was found to stabilize Cdk6 mRNA via 3′-UTR binding to sustain G1/S progression in neural progenitors, with conditional KO causing extended G1, impaired proliferation, and cortical lamination defects.

    Evidence Conditional KO in mouse cortex, CLIP-seq for Cdk6 3′-UTR, mRNA stability assays, cell-cycle labeling

    PMID:40555862

    Open questions at the time
    • Whether Cdk6 is the sole essential target mediating the cortical phenotype not tested by epistasis
    • Interaction with cell-cycle-dependent CSDE1 regulation (IRES at G2/M) not integrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: what determines whether CSDE1 stabilizes versus destabilizes a given mRNA target; what kinases phosphorylate CSDE1 and how this switches its activity; and what is the full-length multi-CSD architecture on RNA.
  • No full-length CSDE1 structure available
  • Rules governing target-specific stabilization versus destabilization unknown
  • Kinase-substrate relationships for CSDE1 phosphorylation not identified
  • Systematic assessment of CSDE1 in miRNA biogenesis beyond miR-451/miR-486 lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 4 GO:0098772 molecular function regulator activity 4 GO:0044183 protein folding chaperone 2
Localization
GO:0005829 cytosol 3 GO:0005840 ribosome 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 2 R-HSA-8953854 Metabolism of RNA 2 R-HSA-168256 Immune System 1
Partners
AGO2MKRN2PABPC1PARNPTBSTRAPSXLTRIM28
Complex memberships
CSDE1-STRAP/UNRIP complexSXL-UNR-PABP translational repression complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 UNR/CSDE1 protein has high affinity for single-stranded DNA or RNA and low affinity for double-stranded nucleic acids, and is predominantly localized in the cytoplasm with partial association with the endoplasmic reticulum, established by nucleic acid binding assays and fractionation. In vitro nucleic acid binding assays, subcellular fractionation, immunolocalization Nucleic acids research High 7518919
1999 UNR/CSDE1 binds purine-rich sequences with a consensus core motif (AAGUA/G or AACG) downstream of a purine stretch, with an apparent Kd of ~10 nM; multiple CSDs are required for high-affinity binding, with CSD1-2-3 and CSD1-2-3-4-5 combinations sufficient for high affinity. In vitro SELEX, RNA binding assays with individual CSD domain constructs Nucleic acids research High 10101203
1999 UNR/CSDE1 is required for internal ribosome entry site (IRES)-dependent translation of human rhinovirus (HRV) RNA; it acts synergistically with PTB to stimulate HRV IRES-dependent translation. UNR interacts with p38/UNRIP (a GH-WD repeat protein), forming a complex recovered by RNA-affinity chromatography from HeLa cell extracts. RNA-affinity purification, co-immunoprecipitation, recombinant protein reconstitution in reticulocyte lysate translation assays Genes & development High 10049359
2003 Loss of UNR/CSDE1 in murine embryonic stem cells (unr−/− ES cells) severely impairs translation directed by the HRV IRES and the poliovirus IRES in vivo; reintroduction of Unr rescues IRES activity, demonstrating Unr as a specific IRES trans-acting factor (ITAF) for enterovirus/rhinovirus subgroup but not EMCV or FMDV. Homologous recombination knockout of unr gene in ES cells, dicistronic reporter assays, rescue by transient expression Journal of virology High 12610110
2003 UNR/CSDE1 and PTB act as RNA chaperones on the Apaf-1 IRES: UNR must prebind first, enabling PTB/nPTB to bind and remodel the IRES structure into a conformation that exposes the ribosome landing site as a single-stranded region, permitting translation initiation. RNA structural probing, mapping of UNR and PTB binding sites on Apaf-1 IRES, functional translation assays in cell-free systems and cell lines Molecular cell High 12667457
2004 UNR/CSDE1 is an mCRD (c-fos major coding-region determinant)-binding protein that also interacts with poly(A)-binding protein (PABP); the UNR-PABP interaction is necessary for the full destabilization function of the mCRD, and UNR associates with the poly(A) nuclease CCR4, coupling mRNA deadenylation/decay to ongoing translation. Co-immunoprecipitation, RNA-protein binding assays, functional mRNA decay assays with translation inhibitors, identification of CCR4 as associated nuclease Genes & development High 15314026
2004 All five cold-shock domains of UNR/CSDE1 are required for RNA binding to the HRV-2 IRES and for stimulation of IRES-dependent translation; point mutations in individual CSDs abolish both RNA binding and translational stimulation. Site-directed mutagenesis of individual CSDs, in vitro RNA binding assays, cell-free translation assays The Journal of general virology High 15269369
2005 The PITSLRE IRES contains a Unr consensus binding site essential for IRES activity; Unr protein binds the PITSLRE IRES and is more prominently expressed at G2/M, where phosphorylation of eIF-2α has a permissive effect on PITSLRE IRES activity. Deletion analysis of IRES, UV cross-linking, cell-cycle-dependent expression analysis, eIF-2α phosphorylation assays The Biochemical journal Medium 15330758
2005 The 5'-UTR of UNR mRNA contains an IRES that is negatively regulated by PTB; PTB binds a pyrimidine-rich region (nt 335-355) in the UNR IRES and overexpression of PTB inhibits UNR IRES activity and UNR protein expression. Unr also negatively regulates its own IRES activity and interacts with its own mRNA in vivo, constituting a feedback loop. Dicistronic reporter assays, UV cross-linking, RNA affinity chromatography, RNAi depletion of PTB, IRES mutagenesis Nucleic acids research High 15928332
2006 In Drosophila, UNR is recruited by the female-specific protein SXL to the 3'-UTR of msl-2 mRNA; this requires SXL binding to uridine-rich sequences in the 3'-UTR, and UNR acts as a corepressor of msl-2 translation to ensure dosage compensation in females. Purification of translationally silenced msl-2 mRNPs, mass spectrometry identification of UNR, co-IP, functional translational repression assays in Drosophila Genes & development High 16452508
2006 Drosophila UNR interacts with SXL and is required for SXL-mediated repression of msl-2 mRNA translation; UNR binds to regulatory sequences in the msl-2 3'-UTR adjacent to SXL-bound uridine-rich sequences, conferring sex-specific translational repression. Co-immunoprecipitation, functional assays of msl-2 translation in Drosophila S2 cells, genetic analysis Genes & development High 16452509
2006 During mitosis, hnRNP C1/C2 proteins stimulate UNR IRES activity by binding to the UNR IRES, while PTB and Unr itself dissociate from the IRES, increasing UNR protein expression. UNR in turn contributes to PITSLRE IRES activity; siRNA knockdown of hnRNP C1/C2 or Unr abrogates or retards mitosis. IRES reporter assays during cell cycle stages, RNA-protein interaction assays, siRNA knockdown with mitosis progression readout The EMBO journal Medium 17159903
2007 UNR/CSDE1 binds to two distinct secondary structure domains of the HRV-2 IRES and acts as an RNA chaperone to maintain the complex tertiary IRES structure required for translational competency. RNA binding site mapping, identification of specific nucleotides by mutagenesis, functional translation assays The Journal of general virology Medium 17947529
2008 The first cold-shock domain (CSD1) of Drosophila UNR is the domain required for interaction with SXL and msl-2 mRNA; three exposed residues within CSD1 are required for complex formation. Translational repression additionally requires the amino-terminal Q-rich stretch and the two first CSDs (first 397 aa), which constitute the translational effector domain. Gel-mobility shift assays with individual CSD domains, site-directed mutagenesis, tethering assays in cell-free translation systems RNA (New York, N.Y.) High 18203923
2009 The SXL-UNR corepressor complex inhibits ribosome recruitment to msl-2 mRNA via a PABP-dependent mechanism: UNR directly interacts with PABP, and the repressor complex acts after PABP-mediated recruitment of eIF4E/G to block ribosome binding. Direct biochemical assays for eIF4F and ribosome recruitment, co-IP of UNR with PABP, functional translation assays with poly(A) tail requirements Molecular cell High 19941818
2010 NMR solution structures of all five CSDs of human UNR were determined; CSD1 has altered sidechain conformations in its RNP-1 and RNP-2 RNA-binding motifs (involving F43, H45, C46, Y30) compared to other CSDs, correlating with its 20-fold higher RNA-binding activity relative to CSD5. Solution NMR structure determination of all five CSDs Journal of structural and functional genomics High 20213426
2011 UNR/CSDE1 prevents differentiation of mouse embryonic stem cells into primitive endoderm by destabilizing Gata6 mRNAs; unr−/− ES cells spontaneously differentiate into PrE and re-expression of Unr reverses this phenotype. Knockout ES cell analysis, mRNA stability assays for Gata6, rescue by re-expression Stem cells (Dayton, Ohio) Medium 21954113
2013 shRNA-mediated knockdown of Csde1 in mice causes failure of precerebellar neurons to complete both tangential and radial migration to their target regions in the hindbrain, establishing a required role for Csde1 in neuronal migration. shRNA knockdown in vivo (mouse), neuronal migration tracking Neuroscience Medium 24012837
2014 Crystal structure (2.8 Å), NMR, and SAXS/SANS data of the ternary Sxl-Unr-msl2 mRNA complex reveal that the first CSD of Unr and two Sxl RRMs form intertwined interactions with RNA; cooperative complex formation increases RNA binding affinity ~1000-fold for the Unr CSD, and novel ternary RNA contacts including non-canonical contacts by the α1 helix of Sxl RRM1 are identified. X-ray crystallography (2.8 Å), NMR, SAXS, SANS Nature High 25209665
2014 Drosophila UNR promotes targeting of the male-specific lethal (MSL) dosage-compensation complex to the X chromosome by facilitating the interaction between the RNA helicase MLE and the long non-coding RNA roX2. Co-immunoprecipitation, RNA-binding assays, functional dosage compensation assays Nature communications Medium 25158899
2016 UNR/CSDE1 stimulates translation in vitro through cold-shock domains 2 and 4, promotes binding of PABP1 to mRNA, and is required for the stable interaction of PABP1 and eIF4G in cells; siRNA knockdown of Unr reduces overall cellular translation and cap-dependent and IRES-dependent reporter translation. In vitro translation assays, CSD domain mutagenesis, co-IP of PABP1/eIF4G, siRNA knockdown with polysome/translation readouts Scientific reports High 26936655
2016 UNR/CSDE1 promotes melanoma invasion and metastasis by post-transcriptionally regulating a pro-metastatic RNA regulon; it controls target mRNAs including VIM and RAC1 at the levels of RNA steady-state and translation elongation/termination, as revealed by iCLIP, RNA-seq, and ribosome profiling. iCLIP-seq, RNA-seq, ribosome profiling, loss- and gain-of-function experiments in melanoma cells and mouse models Cancer cell High 27908735
2017 CSDE1/UNR is highly expressed in human embryonic stem cells and post-transcriptionally modulates core components of hESC identity and neurogenesis; it binds FABP7 and VIM mRNAs and regulates their stability and translation, and loss of CSDE1 accelerates neural differentiation while its ectopic expression impairs it. Loss- and gain-of-function (KO and OE), iCLIP, RNA-seq, ribosome profiling, RIP assays Nature communications High 29129916
2017 UNR/CSDE1 is required in vivo for the formation of nucleoplasmic reticulum (NR) structures in polyploid cells (trophoblast giant cells, hepatocytes); these Unr-NRs are sites of active mRNA translation containing poly(A) RNA and translation factors, and are absent in Unr-null cells. Electron microscopy, live imaging, immunofluorescence with translation factor markers, Unr-null mouse analysis Journal of cell science Medium 28386023
2018 CSDE1 directly interacts with BC200 lncRNA, and STRAP indirectly binds BC200 via heterodimerization with CSDE1; knockdown of BC200 causes redistribution of CSDE1 into nuclear foci, revealing a reciprocal regulatory relationship between CSDE1 and BC200. Mass spectrometry of BC200 RNP, co-IP, RNA truncation binding-site mapping, immunofluorescence after knockdown Nucleic acids research Medium 30247708
2018 Csde1 binds mRNAs encoding proteins involved in protein homeostasis (ribogenesis, translation, protein degradation) in erythroid cells; deletion of CSD1 by CRISPR-Cas9 affects both mRNA and protein expression of Csde1-bound transcripts (e.g., enhanced Pabpc1 protein with reduced Pabpc1 mRNA, suggesting more efficient translation followed by feedback mRNA destabilization). RNA-IP, CRISPR-Cas9 CSD1 deletion, RNA-seq, proteomics Scientific reports Medium 29422612
2018 STRAP/UNRIP (the unr-interacting protein) is the most strongly associated protein with Csde1 in erythroblasts; Strap knockdown alters mRNA and/or protein expression of several Csde1-bound transcripts (Hmbs, eIF4g3, Pabpc4, Vim, Elavl1) without changing the pool of Csde1-bound transcripts. Co-IP/mass spectrometry, Strap knockdown, RNA-seq, proteomics PloS one Medium 30138317
2019 CSDE1 loss-of-function in mouse cortical neurons causes overgrowth of neurites, abnormal dendritic spine morphology, impaired synapse formation, and impaired synaptic transmission; HITS-CLIP shows Csde1-binding targets are enriched in autism-associated and FMRP target gene sets involved in neuronal development and synaptic plasticity. HITS-CLIP, Csde1 knockdown in primary mouse cortical neurons (morphology/synapse readouts), Drosophila mutant synapse assays Science advances High 31579823
2021 CSDE1 interacts with AGO2 (the essential miRISC component) via target mRNAs, dependent on the first cold-shock domain (CSD1) of CSDE1; CSDE1 counters AGO2 binding to the 3'-UTR of PMEPA1, attenuating miR-129-5p/AGO2-mediated silencing of PMEPA1 and increasing PMEPA1 expression in melanoma. Co-IP of CSDE1 with AGO2, RNA-IP, competitive binding assays, CSD domain dependency experiments, functional reporter assays Oncogene High 33833398
2021 CSDE1 promotes STAT1 dephosphorylation by stabilizing T cell protein tyrosine phosphatase (TCPTP) mRNA/protein, thereby reducing tumor immunogenicity; SMYD3 mediates H3K4 trimethylation of the CSDE1 locus via mechanotransduction, linking epigenetic regulation to CSDE1-mediated immune evasion. RNA-seq, CSDE1 overexpression/knockdown, STAT1 phosphorylation assays, chromatin IP for H3K4me3 at CSDE1 locus, TCPTP binding assays Science translational medicine Medium 36724242
2022 UNR/CSDE1 enables oncogene-induced senescence (OIS) in primary mouse keratinocytes by two independent mechanisms: (1) enhancing stability of SASP factor mRNAs and (2) repressing translation of Ybx1 mRNA; depletion of CSDE1 leads to senescence bypass, immortalization, and tumor formation (CSDE1 functions as a tumor suppressor in this context). CSDE1 depletion in primary keratinocytes, high-throughput transcriptomics and translatome profiling, mRNA stability and translation assays, in vivo tumor formation Cell reports High 35021076
2022 The lncRNA ARHGAP5-AS1 stabilizes CSDE1 protein by attenuating interactions between CSDE1 and the E3 ubiquitin ligase TRIM28, preventing CSDE1 degradation via the ubiquitin-proteasome pathway; elevated CSDE1 promotes translation of VIM and RAC1 and activates the ERK pathway in HCC. Co-IP of CSDE1 with TRIM28, ubiquitination assays, lncRNA-protein interaction assays, functional cancer cell assays Clinical and translational medicine Medium 36354136
2022 UNR/CSDE1 interacts with HIV-1 Gag (via its NC domain) and NCp7 as confirmed by co-immunoprecipitation and FRET-FLIM; UNR acts as an ITAF increasing HIV-1 IRES-dependent translation, while NCp7 counteracts this stimulatory effect; Unr knockdown decreases infection by a non-replicative lentivector. Co-immunoprecipitation, FRET-FLIM, dual luciferase IRES assay, IRES point mutation analysis, siRNA knockdown Viruses Medium 36016420
2023 CSDE1 promotes biogenesis of miR-451 in erythroid cells by binding pre-miR-451 and regulating AGO2 processing through its N-terminal domains; CSDE1 further interacts with PARN and promotes trimming of intermediate miR-451 to mature length. RNA-IP, in vitro AGO2 processing assays, domain dependency studies, PARN interaction assays Nucleic acids research Medium 37493604
2023 Csde1 binds ctnnb1 mRNAs (encoding β-catenin) and enhances their translation without altering mRNA stability in zebrafish embryos, thereby increasing β-catenin protein levels and Wnt/β-catenin signaling activity required for HSPC generation during embryonic development. Csde1 genetic mutants and morpholino knockdown in zebrafish, RIP assays for ctnnb1 mRNA, polysome profiling, mRNA stability assays Development (Cambridge, England) Medium 37874038
2025 The Csde1-Strap complex binds Bach2 mRNA and couples its decay with translation to restrain the magnitude and duration of Bach2 protein expression during B-cell differentiation; in the absence of Csde1 or Strap, Bach2 translation is decoupled from mRNA decay, leading to elevated and prolonged Bach2 protein and impaired plasma cell differentiation. RNA interactome capture-coupled CRISPR/Cas9 functional screening, co-IP of Csde1-Strap complex, RIP for Bach2 mRNA, mRNA stability and translation assays in B cells Nature communications High 40133358
2025 CSDE1 is phosphorylated early during melanoma cellular transformation, and this phosphorylation correlates with changes in its subcellular localization and increased interactions with ribosomes; CSDE1 phosphorylation promotes ribosome association in melanoma cells compared to healthy melanocytes. Long-read Nanopore sequencing, 2D gel electrophoresis, interactome proteomics, phosphorylation site mapping, subcellular fractionation RNA (New York, N.Y.) Medium 40883018
2025 CSDE1 directly binds the 3'-UTR of Cdk6 mRNA and maintains its stability, thereby sustaining Cdk6 levels required for the G1/S transition; Csde1 knockout in mouse cortex extends G1 phase duration in neural progenitors, causing impaired proliferation, abnormal cortical lamination, and embryonic lethality. Csde1 conditional KO in mouse cortex, CLIP-seq for 3'-UTR binding, Cdk6 mRNA stability assays, dual thymidine cell cycle labeling Neuroscience bulletin Medium 40555862
2025 CSDE1 stabilizes AGO2 protein in mouse embryonic stem cells by preventing AGO2 ubiquitination; this stabilization is dependent on CSD1 (the first cold-shock domain), and CSDE1 also stabilizes pluripotency proteins NANOG, SOX2, and Oct4. CSDE1 KD/OE, ubiquitination assays for AGO2, CSD1 domain-dependency experiments, Western blotting for pluripotency markers Frontiers in molecular biosciences Medium 41624769
2025 CSDE1 contributes to AGO2-mediated cleavage of the passenger strand miR-486-3p to facilitate miR-486-5p maturation; loss of CSDE1 increases miR-486-3p levels, decreases in vitro cleavage efficiency, and derepresses miR-486-5p targets; the function requires CSD1 for AGO2 interaction. In vitro AGO2 duplex cleavage assays, CSDE1 KO/rescue, miRNA quantification, CSD1 domain analysis RNA biology Medium 41905768
2026 MKRN2 E3 ubiquitin ligase directly ubiquitinates CSDE1 at four lysine residues (K81, K91, K208, K727); MKRN2 and CSDE1 form co-localized condensates via liquid-liquid phase separation, and disruption of either protein abolishes condensate formation; Mkrn2 KO mice show sex-specific social abnormalities consistent with ASD. Mass spectrometry identification of CSDE1 as MKRN2 substrate, mutagenesis of ubiquitination sites, LLPS assays, Mkrn2 KO mouse behavioral assays Frontiers in cellular neuroscience Medium 41757349
2025 CSDE1 enhances genotoxic drug resistance by forming a ternary CSDE1-eIF3a-RPA2 mRNA complex that upregulates RPA2 expression and nucleotide excision repair/homologous recombination pathways; systemic CSDE1 KO in mice increases DNA damage in response to irradiation; CSDE1 inhibits the cGAS-STING pathway through RPA2. Biotin pull-down, EMSA, co-IP for ternary complex characterization, CSDE1 KO mouse models with DNA damage assays, cGAS-STING pathway analysis Drug resistance updates Medium 40398074
1996 UNR/CSDE1 interacts with the N-terminal segment of the ALL-1 (MLL) protein; two CSDs and two intervening polypeptides of UNR constitute the minimal region required for this interaction, confirmed by in vitro binding and co-immunoprecipitation from COS cells. Yeast two-hybrid screening, in vitro binding assays, co-immunoprecipitation Oncogene Medium 8934551

Source papers

Stage 0 corpus · 77 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA. Genes & development 216 10049359
2003 The Apaf-1 internal ribosome entry segment attains the correct structural conformation for function via interactions with PTB and unr. Molecular cell 209 12667457
2004 UNR, a new partner of poly(A)-binding protein, plays a key role in translationally coupled mRNA turnover mediated by the c-fos major coding-region determinant. Genes & development 130 15314026
2016 UNR/CSDE1 Drives a Post-transcriptional Program to Promote Melanoma Invasion and Metastasis. Cancer cell 125 27908735
2014 Structural basis for the assembly of the Sxl-Unr translation regulatory complex. Nature 99 25209665
2003 Unr is required in vivo for efficient initiation of translation from the internal ribosome entry sites of both rhinovirus and poliovirus. Journal of virology 99 12610110
2006 A role for hnRNP C1/C2 and Unr in internal initiation of translation during mitosis. The EMBO journal 88 17159903
2006 Sex-lethal imparts a sex-specific function to UNR by recruiting it to the msl-2 mRNA 3' UTR: translational repression for dosage compensation. Genes & development 76 16452508
2005 Regulation of the cell-cycle-dependent internal ribosome entry site of the PITSLRE protein kinase: roles of Unr (upstream of N-ras) protein and phosphorylated translation initiation factor eIF-2alpha. The Biochemical journal 76 15330758
1999 RNA binding specificity of Unr, a protein with five cold shock domains. Nucleic acids research 67 10101203
2005 UNR translation can be driven by an IRES element that is negatively regulated by polypyrimidine tract binding protein. Nucleic acids research 63 15928332
2009 The SXL-UNR corepressor complex uses a PABP-mediated mechanism to inhibit ribosome recruitment to msl-2 mRNA. Molecular cell 62 19941818
2006 Drosophila UNR is required for translational repression of male-specific lethal 2 mRNA during regulation of X-chromosome dosage compensation. Genes & development 62 16452509
1994 Nucleic acid binding and intracellular localization of unr, a protein with five cold shock domains. Nucleic acids research 61 7518919
2017 A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nature communications 60 29129916
1990 Characterization of unr; a gene closely linked to N-ras. Nucleic acids research 56 2204029
2020 The role of CSDE1 in translational reprogramming and human diseases. Cell communication and signaling : CCS 49 31987048
1997 Transcription of unr (upstream of N-ras) down-modulates N-ras expression in vivo. FEBS letters 46 9450542
2006 Unr, a cytoplasmic RNA-binding protein with cold-shock domains, is involved in control of apoptosis in ES and HuH7 cells. Oncogene 44 17086213
2005 MicroPET imaging of MCF-7 tumors in mice via unr mRNA-targeted peptide nucleic acids. Bioconjugate chemistry 44 15769082
2011 The RNA-binding protein Unr prevents mouse embryonic stem cells differentiation toward the primitive endoderm lineage. Stem cells (Dayton, Ohio) 43 21954113
2022 N6 -methyladenosine-modified lncRNA ARHGAP5-AS1 stabilises CSDE1 and coordinates oncogenic RNA regulons in hepatocellular carcinoma. Clinical and translational medicine 40 36354136
2019 Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. Science advances 37 31579823
2007 Internal initiation of translation from the human rhinovirus-2 internal ribosome entry site requires the binding of Unr to two distinct sites on the 5' untranslated region. The Journal of general virology 36 17947529
1992 The product of unr, the highly conserved gene upstream of N-ras, contains multiple repeats similar to the cold-shock domain (CSD), a putative DNA-binding motif. The New biologist 34 1622933
2019 UNR/CSDE1 Expression Is Critical to Maintain Invasive Phenotype of Colorectal Cancer through Regulation of c-MYC and Epithelial-to-Mesenchymal Transition. Journal of clinical medicine 32 31027221
2005 Regulation of Unr expression by 5'- and 3'-untranslated regions of its mRNA through modulation of stability and IRES mediated translation. RNA biology 30 17114922
2023 Epigenetic modification of CSDE1 locus dictates immune recognition of nascent tumorigenic cells. Science translational medicine 29 36724242
2014 UNR facilitates the interaction of MLE with the lncRNA roX2 during Drosophila dosage compensation. Nature communications 27 25158899
2021 Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy. Nature communications 24 33772027
2022 Coordinated post-transcriptional control of oncogene-induced senescence by UNR/CSDE1. Cell reports 23 35021076
2008 Functional domains of Drosophila UNR in translational control. RNA (New York, N.Y.) 23 18203923
2020 LINC00205 promotes malignancy in lung cancer by recruiting FUS and stabilizing CSDE1. Bioscience reports 20 32808651
2013 The control of precerebellar neuron migration by RNA-binding protein Csde1. Neuroscience 20 24012837
2004 All five cold-shock domains of unr (upstream of N-ras) are required for stimulation of human rhinovirus RNA translation. The Journal of general virology 20 15269369
2021 CSDE1 attenuates microRNA-mediated silencing of PMEPA1 in melanoma. Oncogene 19 33833398
2017 Unr defines a novel class of nucleoplasmic reticulum involved in mRNA translation. Journal of cell science 19 28386023
2015 Regulation of the expression and activity of Unr in mammalian cells. Biochemical Society transactions 19 26614667
2011 Widespread generation of alternative UTRs contributes to sex-specific RNA binding by UNR. RNA (New York, N.Y.) 19 22101243
1993 Exon skipping in the expression of the gene immediately upstream of N-ras (unr/NRU). Biochimica et biophysica acta 19 8439573
2018 Csde1 binds transcripts involved in protein homeostasis and controls their expression in an erythroid cell line. Scientific reports 18 29422612
2018 Comprehensive analysis of the BC200 ribonucleoprotein reveals a reciprocal regulatory function with CSDE1/UNR. Nucleic acids research 18 30247708
2021 Wnt/β-catenin pathway and cell adhesion deregulation in CSDE1-related intellectual disability and autism spectrum disorders. Molecular psychiatry 17 33867523
2015 Hepsin inhibits CDK11p58 IRES activity by suppressing unr expression and eIF-2α phosphorylation in prostate cancer. Cellular signalling 17 25576733
2001 Murine leukemia virus proviral insertions between the N-ras and unr genes in B-cell lymphoma DNA affect the expression of N-ras only. Journal of virology 17 11689675
2016 Stimulation of translation by human Unr requires cold shock domains 2 and 4, and correlates with poly(A) binding protein interaction. Scientific reports 16 26936655
1999 The unr gene: evolutionary considerations and nucleic acid-binding properties of its long isoform product. DNA and cell biology 16 10098602
2022 Reduced miR-371b-5p expression drives tumor progression via CSDE1/RAC1 regulation in triple-negative breast cancer. Oncogene 14 35490208
2010 The NMR solution structures of the five constituent cold-shock domains (CSD) of the human UNR (upstream of N-ras) protein. Journal of structural and functional genomics 13 20213426
2023 CSDE1 promotes miR-451 biogenesis. Nucleic acids research 12 37493604
2021 The CDT of Helicobacter hepaticus induces pro-survival autophagy and nucleoplasmic reticulum formation concentrating the RNA binding proteins UNR/CSDE1 and P62/SQSTM1. PLoS pathogens 12 33662035
2005 Identification and characterization of high affinity antisense PNAs for the human unr (upstream of N-ras) mRNA which is uniquely overexpressed in MCF-7 breast cancer cells. Nucleic acids research 12 16314303
2018 Strap associates with Csde1 and affects expression of select Csde1-bound transcripts. PloS one 11 30138317
2018 RNA-binding Protein UNR Promotes Glioma Cell Migration and Regulates the Expression of Ribosomal Protein L9. Chinese medical sciences journal = Chung-kuo i hsueh k'o hsueh tsa chih 11 30266104
1996 ALL-1 interacts with unr, a protein containing multiple cold shock domains. Oncogene 11 8934551
1992 Organization of the unr/N-ras locus: characterization of the promoter region of the human unr gene. Nucleic acids research 10 1475196
2020 Cold Shock Domain Containing E1 (CSDE1) Protein is Overexpressed and Can be Targeted to Inhibit Invasiveness in Pancreatic Cancer Cells. Proteomics 9 32170829
2018 miR-132 and miR-212 cluster function as a tumor suppressor in thyroid cancer cells by CSDE1 mediated post-transcriptional program. International journal of clinical and experimental pathology 8 31938190
2021 A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents. American journal of medical genetics. Part A 6 34519148
2022 A de novo truncating variant in CSDE1 in an adult-onset neuropsychiatric phenotype without intellectual disability. European journal of medical genetics 4 35026469
2024 Leader RNA facilitates snakehead vesiculovirus (SHVV) replication by interacting with CSDE1 and hnRNP A3. Fish & shellfish immunology 3 39341378
2022 Upstream of N-Ras (Unr/CSDE1) Interacts with NCp7 and Gag, Modulating HIV-1 IRES-Mediated Translation Initiation. Viruses 3 36016420
2025 A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay. Nature communications 2 40133358
2023 The RNA-binding protein CSDE1 promotes hematopoietic stem and progenitor cell generation via translational control of Wnt signaling. Development (Cambridge, England) 2 37874038
2013 Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. PloS one 2 23418499
2025 Csde1 Mediates Neurogenesis via Post-transcriptional Regulation of the Cell Cycle. Neuroscience bulletin 1 40555862
2025 CSDE1 regulates the miR-20a-5p/TMBIM6 axis in melanoma. RNA (New York, N.Y.) 1 41093770
2026 CSDE1 stabilizes AGO2 in embryonic stem cells. Frontiers in molecular biosciences 0 41624769
2026 Liquid-liquid phase separation couples MKRN2-mediated ubiquitination of CSDE1 with neurodevelopmental disorders. Frontiers in cellular neuroscience 0 41757349
2026 CSDE1 Drives Glycolysis and the Progression of Prostate Cancer Through RAC1-Dependent RAS/MAPK Activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41808419
2026 CSDE1-mediated histone lactylation modification of the HOXD9 promoter promotes gastric cancer progression. Biochemical pharmacology 0 41864431
2026 CSDE1 promotes passenger strand cleavage of miR-486. RNA biology 0 41905768
2025 CSDE1 enhances genotoxic drug resistance in cancer by modulating RPA2 through CSDE1-eIF3a regulatory complex. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 0 40398074
2025 Context-dependent phosphorylation of CSDE1 drives interactions with ribosomes. RNA (New York, N.Y.) 0 40883018
2025 CSDE1 depletion inhibits tumor progression through enhancing B-cell infiltration in NSCLC. Cell death & disease 0 41353256
2024 High-resolution RNA-sequencing reveals TRIM33 :: CSDE1 gene fusion in metastasizing vulvar melanoma. Melanoma research 0 39291968
2024 Flow Cytometry Analysis of Perturbations in the Bacterial Cell Envelope Enabled by Monitoring Generalized Polarization of the Solvatochromic Peptide UNR-1. Analytical chemistry 0 39810345