# CELF1 is a non-canonical eIF4E binding protein that promotes translation of epithelial-mesenchymal transition effector mRNAs **Authors:** Arindam Chaudhury, Natee Kongchan, Shebna A Massey, Rajesh Sharma, Rituraj Pal, Na Zhao, Phoebe Tsoi, Yingmin Zhu, Emuejevoke Olokpa, Sufeng Mao, Sonia del Rincon, Lucas C Reineke, Richard E Lloyd, Marco Sardiello, Jeffrey M Rosen, Choel Kim, Josephine C Ferreon, Joel R Neilson PMC · DOI: 10.1093/nar/gkag123 · Nucleic Acids Research · 2026-02-27 ## TL;DR The study shows how CELF1 promotes translation of specific mRNAs during cell transformation, using a non-standard pathway involving eIF4E and PABPC1. ## Contribution The paper identifies a novel non-canonical translation mechanism involving CELF1, eIF4E, and PABPC1 that regulates epithelial-mesenchymal transition. ## Key findings - CELF1 binds eIF4E and PABPC1 to promote translation of GRE-containing mRNAs independently of eIF4G1. - Disrupting the CELF1/eIF4E interaction inhibits epithelial-mesenchymal transition and metastasis in vivo. ## Abstract Mounting evidence is revealing an increasing complexity of gene regulation at the level of messenger RNA (mRNA) translation. Within mammalian cells, canonical cap-dependent mRNA translation depends on the eIF4F complex, consisting of the m7G mRNA cap-binding protein eukaryotic initiation factor 4E (eIF4E), the helicase eIF4A (eIF4A), and the eIF4G (eIF4G1) scaffolding protein. eIF4G1 additionally binds poly(A) binding protein (PABPC1) to facilitate mRNA circularization and nucleates pre-translation initiation complex assembly to initiate ribosomal scanning. In breast epithelial cells, the CELF1 RNA-binding protein specifically promotes the translation of select epithelial-to-mesenchymal transition (EMT) effector mRNAs by binding GU-rich elements (GREs) within their 3′ untranslated regions (UTRs). Here we show that CELF1 directly binds to both eIF4E and PABPC1 to promote eIF4G1-independent translation of GRE-containing mRNAs in mesenchymal cells. Disruption of this CELF1/eIF4E interaction inhibits both EMT induction in vitro and experimental metastasis in vivo. Our findings define a novel, non-canonical mode of translational regulation underlying cellular de-differentiation, raising the possibility that analogous non-canonical modes of translation impact additional transitional cellular states within development and disease. Graphical Abstract ## Linked entities - **Genes:** CELF1 (CUGBP Elav-like family member 1) [NCBI Gene 10658], EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977], EIF4A1 (eukaryotic translation initiation factor 4A1) [NCBI Gene 1973], EIF4G1 (eukaryotic translation initiation factor 4 gamma 1) [NCBI Gene 1981], PABPC1 (poly(A) binding protein cytoplasmic 1) [NCBI Gene 26986] - **Proteins:** CELF1 (CUGBP Elav-like family member 1), EIF4E (eukaryotic translation initiation factor 4E), EIF4A1 (eukaryotic translation initiation factor 4A1), EIF4G1 (eukaryotic translation initiation factor 4 gamma 1), PABPC1 (poly(A) binding protein cytoplasmic 1) - **Diseases:** breast cancer (MONDO:0004989) - **Species:** Mus musculus (taxon 10090) ## Full-text entities - **Genes:** EIF5 (eukaryotic translation initiation factor 5) [NCBI Gene 1983] {aka EIF-5, EIF-5A}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, eIF4G1 (eukaryotic translation initiation factor 4G1) [NCBI Gene 43839] {aka CG10811, Dmel\CG10811, EIF4G, Eif4G, deIF4G, eIF-4G}, SLTM (SAFB like transcription modulator) [NCBI Gene 79811] {aka Met}, PRL (prolactin) [NCBI Gene 5617] {aka GHA1, pPRL}, EIF2S2 (eukaryotic translation initiation factor 2 subunit beta) [NCBI Gene 8894] {aka EIF2, EIF2B, EIF2beta, PPP1R67, eIF-2-beta}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, ThrRS (Threonyl-tRNA synthetase) [NCBI Gene 45784] {aka 2L16, 42/3, Aats-thr, CG5353, Dmel\CG5353, P539}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, eIF4E1 (eukaryotic translation initiation factor 4E1) [NCBI Gene 45525] {aka 0260/09, 0587/11, 0589/11, 0919/12, 1004/13, 2}, CRLF1 (cytokine receptor like factor 1) [NCBI Gene 9244] {aka CISS, CISS1, CLF, CLF-1, NR6, zcytor5}, EIF4E (eukaryotic translation initiation factor 4E) [NCBI Gene 1977] {aka AUTS19, CBP, EIF4E1, EIF4EL1, EIF4F, eIF-4E}, CELF1 (CUGBP Elav-like family member 1) [NCBI Gene 10658] {aka BRUNOL2, CUG-BP, CUGBP, CUGBP1, EDEN-BP, NAB50}, mxt (mextli) [NCBI Gene 33686] {aka BcDNA:GH06479, CG2950, Dmel\CG2950, cg2950}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, GLB1 (galactosidase beta 1) [NCBI Gene 2720] {aka EBP, ELNR1, MPS4B}, NGDN (neuroguidin) [NCBI Gene 25983] {aka C14orf120, CANu1, LCP5, NGD, lpd-2}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, CDKN3 (cyclin dependent kinase inhibitor 3) [NCBI Gene 1033] {aka CDI1, CIP2, KAP, KAP1}, EIF1 (eukaryotic translation initiation factor 1) [NCBI Gene 10209] {aka A121, EIF-1, EIF1A, ISO1, SUI1}, EIF4G1 (eukaryotic translation initiation factor 4 gamma 1) [NCBI Gene 1981] {aka EIF-4G1, EIF4F, EIF4G, EIF4GI, P220, PARK18}, EIF4G2 (eukaryotic translation initiation factor 4 gamma 2) [NCBI Gene 1982] {aka AAG1, DAP5, NAT1, P97}, CELF2 (CUGBP Elav-like family member 2) [NCBI Gene 10659] {aka BRUNOL3, CELF-2, CUG-BP2, CUGBP2, DEE97, ETR-3}, MTG1 (mitochondrial ribosome associated GTPase 1) [NCBI Gene 92170] {aka GTP, GTPBP7}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, ACTB (actin beta) [NCBI Gene 60] {aka BKRNS, BNS, BRWS1, CSMH, DDS1, PS1TP5BP1}, EIF4G3 (eukaryotic translation initiation factor 4 gamma 3) [NCBI Gene 8672] {aka eIF-4G 3, eIF4G 3, eIF4GII}, EGR3 (early growth response 3) [NCBI Gene 1960] {aka EGR-3, PILOT}, POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, Pabpc1 (poly(A) binding protein, cytoplasmic 1) [NCBI Gene 18458] {aka PABP, Pabp1, PabpI, Pabpl1, ePAB}, PABPC1 (poly(A) binding protein cytoplasmic 1) [NCBI Gene 26986] {aka PAB1, PABP, PABP1, PABPC2, PABPL1}, CDKN1A (cyclin dependent kinase inhibitor 1A) [NCBI Gene 1026] {aka CAP20, CDKN1, CIP1, MDA-6, P21, SDI1}, SSBP2 (single stranded DNA binding protein 2) [NCBI Gene 23635] {aka HSPC116, SOSS-B2}, CEBPD (CCAAT enhancer binding protein delta) [NCBI Gene 1052] {aka C/EBP-delta, CELF, CRP3, NF-IL6-beta}, Eif4e (eukaryotic translation initiation factor 4E) [NCBI Gene 13684] {aka EG668879, Eif4e-ps, If4e, eIF-4E}, Celf1 (CUGBP, Elav-like family member 1) [NCBI Gene 13046] {aka 1600010O03Rik, Brunol2, CUG-BP, CUG-BP1, CUGBP, Cugbp1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CEBPB (CCAAT enhancer binding protein beta) [NCBI Gene 1051] {aka C/EBP-beta, IL6DBP, NF-IL6, TCF5}, EIF4B (eukaryotic translation initiation factor 4B) [NCBI Gene 1975] {aka EIF-4B, PRO1843}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, MYC (MYC proto-oncogene, bHLH transcription factor) [NCBI Gene 4609] {aka MRTL, MYCC, bHLHe39, c-Myc}, RNASE1 (ribonuclease A family member 1, pancreatic) [NCBI Gene 6035] {aka RAC1, RIB1, RNS1}, eIF4A (eukaryotic translation initiation factor 4A) [NCBI Gene 33835] {aka 2439, 9075, CG9075, Dm-eIF4A, DmRH2, Dmel\CG9075}, EIF3A (eukaryotic translation initiation factor 3 subunit A) [NCBI Gene 8661] {aka EIF3, EIF3S10, P167, TIF32, eIF3-p170, eIF3-theta}, EIF3C (eukaryotic translation initiation factor 3 subunit C) [NCBI Gene 8663] {aka EIF3S8, eIF3-p110}, FOSB (FosB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2354] {aka AP-1, G0S3, GOS3, GOSB}, Eif4b (eukaryotic translation initiation factor 4B) [NCBI Gene 75705] {aka 2310046H11Rik, Eif4a2}, EIF4A1 (eukaryotic translation initiation factor 4A1) [NCBI Gene 1973] {aka DDX2A, EIF-4A, EIF4A, eIF-4A-I, eIF4A-I}, VIM (vimentin) [NCBI Gene 7431], EIF4E2 (eukaryotic translation initiation factor 4E family member 2) [NCBI Gene 9470] {aka 4E-LP, 4EHP, EIF4EL3, IF4e, h4EHP}, EIF3H (eukaryotic translation initiation factor 3 subunit H) [NCBI Gene 8667] {aka EIF3S3, eIF3-gamma, eIF3-p40}, eIF3g1 (eukaryotic translation initiation factor 3 subunit g1) [NCBI Gene 31243] {aka CG8636, Dmel\CG8636, cg8636, eIF s4, eIF-3, eIF-3ga}, EIF4A2 (eukaryotic translation initiation factor 4A2) [NCBI Gene 1974] {aka BM-010, DDX2B, EIF4A, EIF4F, NEDHSS, eIF-4A-II} - **Diseases:** triple-negative breast cancer (MESH:D064726), breast cancer (MESH:D001943), lung metastasis (MESH:D009362), T-cell-deficient (MESH:D016399), infection (MESH:D007239), tumorigenesis (MESH:D063646), Cancer (MESH:D009369) - **Chemicals:** luciferin (MESH:D000090562), IPTG (MESH:D007544), m7GTP (MESH:C017516), glutathione (MESH:D005978), paraformaldehyde (MESH:C003043), agarose (MESH:D012685), PBS (MESH:D007854), eosin (MESH:D004801), KCl (MESH:D011189), spermidine (MESH:D013095), DAPI (MESH:C007293), D-glucose (MESH:D005947), Poly(A) (MESH:D011061), GenDEPOT (-), H&E (MESH:D006371), GST (MESH:C059555), hematoxylin (MESH:D006416), HEPES (MESH:D006531), puromycin (MESH:D011691), glycerol (MESH:D005990), Lipofectamine 2000 (MESH:C086724), amino acids (MESH:D000596), creatine phosphate (MESH:D010725), water (MESH:D014867), D2O (MESH:D017666), amide (MESH:D000577), carbenicillin (MESH:D002228), CaCl2 (MESH:D002122), DTT (MESH:D004229), HCl (MESH:D006851), magnesium acetate (MESH:C000656591), SDS (MESH:D012967), MgCl2 (MESH:D015636), potassium acetate (MESH:D019347), NaCl (MESH:D012965), Coomassie Blue R250 (MESH:C024757), phosphate (MESH:D010710), Blasticidin (MESH:C004500), 7-methylguanosine (MESH:C016578), NP-40 (MESH:C010615), EDTA (MESH:D004492), Triton X-100 (MESH:D017830) - **Species:** Gallus gallus (bantam, species) [taxon 9031], Drosophila melanogaster (fruit fly, species) [taxon 7227], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], Encephalomyocarditis virus (no rank) [taxon 12104], Coxsackievirus (species) [taxon 12066], Escherichia coli (E. coli, species) [taxon 562], Mus musculus (house mouse, species) [taxon 10090] - **Mutations:** S209D, W73A, I79A, C with 10, S209A, I63A, serine 209 - **Cell lines:** BL21(DE3) — Mus musculus (Mouse), Hybridoma (CVCL_B7HM), pGEX-5X — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_2768), MCF-10A — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), BL21 Star (DE3) — Canis lupus familiaris (Dog), Canine mammary carcinoma, Cancer cell line (CVCL_B7H9), MCF-10AT1 — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_WM99), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), HEK-293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), MDA-MB-468 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0419) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12956340/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956340/full.md ## References 67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956340/full.md --- Source: https://tomesphere.com/paper/PMC12956340