Mapping of CELF1–RNA interactions reveals post-transcriptional control of lens development
Abstract
Precise post-transcriptional regulation of gene expression is essential for vertebrate lens development. Disruption of the gene encoding the RNA-binding protein CELF1 leads to early-onset cataract in mice. Here, using iCLIP-seq in lenses, we mapped transcriptome-wide CELF1-binding sites, revealing interactions with the 3'UTRs of key transcripts involved in lens development and pathology like Gja8, Jag1, Maf, Pax6, or Prox1. Integrated analysis with transcriptomic data and luciferase reporter assays demonstrated that binding of CELF1 protein represses its target mRNAs by destabilizing transcripts and/or inhibiting their translation. Indeed, the cataract-linked genes Maf and Gja8 are upregulated in Celf1-cKO lenses. In Xenopus laevis, overexpression of maf resulted in abnormal lens structure and eye morphology, confirming the developmental relevance of CELF1-mediated repression. Our findings uncover a post-transcriptional network in which CELF1 controls lens morphogenesis by limiting the expression of critical genes at the mRNA level to achieve their proper dosage.
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BibTeX
@article{viet2026mapping,
title = {{Mapping of CELF1–RNA interactions reveals post-transcriptional control of lens development}},
author = {Justine Viet and Matthieu Duot and Agnès Méreau and Yann Audic and Iwan Jan and David Reboutier and Catherine Le Goff-Gaillard and Sarah Y. Coomson and Salil A. Lachke and Carole Gautier-Courteille and Luc Paillard},
journal = {NAR Molecular Medicine},
year = {2026},
month = aug,
doi = {10.1093/narmme/ugag037},
url = {https://hal.science/hal-05746918v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mapping of CELF1–RNA interactions reveals post-transcriptional control of lens development
AU - Justine Viet
AU - Matthieu Duot
AU - Agnès Méreau
AU - Yann Audic
AU - Iwan Jan
AU - David Reboutier
AU - Catherine Le Goff-Gaillard
AU - Sarah Y. Coomson
AU - Salil A. Lachke
AU - Carole Gautier-Courteille
AU - Luc Paillard
PY - 2026
DA - 2026/08/05
JO - NAR Molecular Medicine
DO - 10.1093/narmme/ugag037
UR - https://hal.science/hal-05746918v1
AB - Precise post-transcriptional regulation of gene expression is essential for vertebrate lens development. Disruption of the gene encoding the RNA-binding protein CELF1 leads to early-onset cataract in mice. Here, using iCLIP-seq in lenses, we mapped transcriptome-wide CELF1-binding sites, revealing interactions with the 3'UTRs of key transcripts involved in lens development and pathology like Gja8, Jag1, Maf, Pax6, or Prox1. Integrated analysis with transcriptomic data and luciferase reporter assays demonstrated that binding of CELF1 protein represses its target mRNAs by destabilizing transcripts and/or inhibiting their translation. Indeed, the cataract-linked genes Maf and Gja8 are upregulated in Celf1-cKO lenses. In Xenopus laevis, overexpression of maf resulted in abnormal lens structure and eye morphology, confirming the developmental relevance of CELF1-mediated repression. Our findings uncover a post-transcriptional network in which CELF1 controls lens morphogenesis by limiting the expression of critical genes at the mRNA level to achieve their proper dosage.
SN - 2976-856X
ER -