Dataset Information

The GC-rich element withing the 5'UTR of β-catenin mRNa modulates its translation under hypoxia

ABSTRACT: Protein synthesis is a universal process mainly regulated at the initiation stage to permit a rapid and reversible control of cellular and environmental changes. Several stress conditions such as hypoxia, activate the translational reprogramming of mRNAs encoding proteins essential for stress recovery and cell survival. Increasing evidence of unconventional translation initiation mechanisms lead by 5’UTR motifs, shows the cells potential to adapt their translation machinery in response to different stimuli. β-catenin is an oncogenic protein playing an essential role in Wnt signal transduction. Dysregulation of this pathway causes aberrant nuclear β-catenin accumulation, which consequently modulates the expression of genes related to cancer development and metastasis. To date, the mechanism of its translation maintenance in stressed cells remains elusive. To understand how β-catenin mRNA escapes global translational blockade in hypoxic cancer cells, we determined the 5’UTR secondary structure and searched for translation regulatory elements in living cells. We found that a three-way junction (TWJ) within its 5’UTR is involved in the translation efficiency (TE) of β-catenin and its enhancement under hypoxia. We showed that the TWJ single-stranded polypurine region becomes, in the absence of eIF4E, an alternative anchoring site for eIF4B, eIF4A and eIF4G. Importantly, the TWJ makes the β-catenin mRNA translation eIF4A-dependent being sensible to silvestrol, a selective eIF4A inhibitor and promising anticancer agent. Our study unravels the 5’UTR-driven translation regulation mechanism of β-catenin mRNA and set the basis to explore its inhibition in the frame of cancer progression.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Johana Chicher

LAB HEAD: Angelita Simonetti

PROVIDER: PXD045451 | Pride | 2025-05-06

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2020_S44_JMoreno_EIF_Hela_CTRL4dil4.mgf	Mgf
	2020_S44_JMoreno_EIF_Hela_CTRL4dil4.raw	Raw
	2020_S44_JMoreno_EIF_Hela_dil4_Hypoxie10.mgf	Mgf
	2020_S44_JMoreno_EIF_Hela_dil4_Hypoxie10.raw	Raw
	2020_S44_JMoreno_EIF_Hela_dil4_Hypoxie8.mgf	Mgf

Items per page:

1 - 5 of 37

Publications

A structural element within the 5'UTR of β-catenin mRNA modulates its translation under hypoxia.

D'Agostino Mattia M Rol-Moreno Javier J Bec Guillaume G Kuhn Lauriane L Ennifar Eric E Simonetti Angelita A

Nucleic acids research 20250401 8

Tight regulation of translation initiation is crucial for cellular adaptation to environmental changes. Stress conditions like hypoxia trigger translational reprogramming of mRNAs encoding proteins essential for stress recovery and cell survival. Recent studies highlight alternative translation initiation pathways based on specific motifs in mRNA 5' untranslated regions (5'UTRs). Notably, β-catenin is of particular interest since maintaining its translation promotes cancer cell persistence and p ...[more]

PMID: 40309781

Similar Datasets

Project description:DEAD-box RNA helicases eIF4A and Ded1 are believed to promote translation initiation by resolving mRNA secondary structures that impede ribosome attachment at the mRNA 5’ end or subsequent scanning of the 5’UTR, but whether they perform distinct functions or act redundantly in vivo is poorly understood. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in yeast by ribosome footprint profiling. Despite similar reductions in bulk translation, inactivation of a cold-sensitive Ded1 mutant substantially reduced the TEs of >600 mRNAs, whereas inactivation of a temperature-sensitive eIF4A mutant yielded <40 similarly impaired mRNAs. The broader requirement for Ded1 did not reflect more pervasive secondary structures at low temperature, as inactivation of temperature-sensitive and cold-sensitive ded1 mutants gave highly correlated results. Interestingly, Ded1-dependent mRNAs exhibit greater than average 5’UTR length and propensity for secondary structure, implicating Ded1 in scanning though structured 5' UTRs. Reporter assays confirmed that cap- distal stem-loop insertions increase dependence on Ded1 but not eIF4A for efficient translation. While only a small fraction of mRNAs is strongly dependent on eIF4A, this dependence is significantly correlated with requirements for Ded1 and 5’UTR features characteristic of Ded1- dependent mRNAs. Our findings suggest that Ded1 is critically required to promote scanning through secondary structures within 5’UTRs; and while eIF4A cooperates with Ded1 in this function, it also promotes a step of initiation common to virtually all yeast mRNAs. We compared the effects of mutations in Ded1 or eIF4A on global translational efficiencies (TEs) in yeast by ribosome footprint profiling.The study includes 32 samples, comprised of 16 mRNA-Seq samples and 16 ribosome footprint profiling samples, derived from biological replicates of 3 mutant strains, ded1-cs, ded1-ts and tif1-ts, and the corresponding wild-type strains. The tif1-ts mutant and its wild-type counterpart were analyzed at 30°C and 37°C.