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

Language

English

Publication Date

2-24-2026

Journal

Nucleic Acids Research

DOI

10.1093/nar/gkag123

PMID

41755641

PMCID

PMC12956340

PubMedCentral® Posted Date

2-27-2026

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Epithelial-Mesenchymal Transition, Humans, CELF1 Protein, RNA, Messenger, Eukaryotic Initiation Factor-4E, Protein Biosynthesis, Eukaryotic Initiation Factor-4G, Poly(A)-Binding Protein I, Animals, 3' Untranslated Regions, Protein Binding, Cell Line, Tumor, Female

Published Open-Access

yes

Recommended Citation

Chaudhury, Arindam; Kongchan, Natee; Massey, Shebna A; et al., "CELF1 Is a Non-Canonical eIF4E Binding Protein That Promotes Translation of Epithelial-Mesenchymal Transition Effector mRNAs" (2026). Faculty, Staff and Students Publications. 6979.
https://digitalcommons.library.tmc.edu/baylor_docs/6979