2026/05/07 by Ting Cai, Nelly M. Cruz, Sudipto Basu +2 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · #Wnt/β-catenin signaling in development and cancer #Developmental Biology and Gene Regulation #Skin and Cellular Biology Research
paper · doi:10.64898/2026.05.05.723075
Abstract Stem cell differentiation depends on transcription factors that are often encoded by mRNAs with highly conserved 3′UTRs. To determine their functional roles, we performed 3′UTR loss-of-function studies. Partial deletion of endogenous 3′UTRs altered stem cell differentiation efficiency in 7/10 cases. As 6/7 3′UTR deletions did not affect expression level of the encoded proteins, we reveal widespread abundance-independent regulatory roles of 3′UTRs. For example, 3′UTR deletion of CTNNB1 , an mRNA that encodes the essential Wnt co-activator β-catenin, keeps β-catenin levels unaffected but impairs zebrafish embryogenesis and induction of the Wnt transcriptional program during human stem cell differentiation. We show that long intermolecular 3′UTR-3′UTR interactions between Wnt transcription factor mRNAs and CTNNB1 enable co-translational protein complex assembly of these transcription factors with β-catenin. As antisense oligonucleotide-mediated blocking of 3′UTR interactions impairs Wnt program induction, our findings indicate that transcriptional regulators can form functional units during protein biogenesis to be fully active.