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The regulatory landscape of 5′ UTRs in translational control during zebrafish embryogenesis

2025; Elsevier BV; Linguagem: Inglês

10.1016/j.devcel.2024.12.038

1878-1551

Madalena M. Reimão-Pinto, Sebastian M. Castillo-Hair, Georg Seelig, Alexander F. Schier,

RNA Research and Splicing

The 5' UTRs of mRNAs are critical for translation regulation during development, but their in vivo regulatory features are poorly characterized. Here, we report the regulatory landscape of 5' UTRs during early zebrafish embryogenesis using a massively parallel reporter assay of 18,154 sequences coupled to polysome profiling. We found that the 5' UTR suffices to confer temporal dynamics to translation initiation and identified 86 motifs enriched in 5' UTRs with distinct ribosome recruitment capabilities. A quantitative deep learning model, Danio Optimus 5-Prime (DaniO5P), identified a combined role for 5' UTR length, translation initiation site context, upstream AUGs, and sequence motifs on ribosome recruitment. DaniO5P predicts the activities of maternal and zygotic 5' UTR isoforms and indicates that modulating 5' UTR length and motif grammar contributes to translation initiation dynamics. This study provides a first quantitative model of 5' UTR-based translation regulation in development and lays the foundation for identifying the underlying molecular effectors.