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

Journal: Developmental cell
Published Date: Jan 15, 2025

Abstract

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.

Authors

  • Madalena M Reimão-Pinto
    Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address: madalena.pinto@unibas.ch.
  • Sebastian M Castillo-Hair
    Department of Electrical & Computer Engineering, University of Washington, Seattle, WA 98195, USA; eScience Institute, University of Washington, Seattle, WA 98195, USA.
  • Georg Seelig
    Department of Electrical & Computer Engineering, University of Washington, Seattle, WA 98195, USA; Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA. Electronic address: gseelig@uw.edu.
  • Alexander F Schier
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA; Biozentrum, University of Basel, 4056 Basel, Switzerland.

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