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Organisms adapt to changing conditions through translational reprogramming. This study reveals that specific RNA structures downstream of upstream start codons (uAUGs) control translation initiation, a mechanism conserved across kingdoms.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Translational reprogramming enables adaptation to environmental changes.
  • Upstream start codons (uAUGs) in messenger RNAs (mRNAs) regulate translation by offering alternative start sites.
  • Mechanisms governing selective translation initiation under different conditions are not fully understood.

Purpose of the Study:

  • To investigate the regulation of selective translation initiation during pattern-triggered immunity in Arabidopsis.
  • To identify the role of upstream open reading frames (uORFs) and associated RNA structures in translational control.
  • To explore the conservation and dynamic regulation of this mechanism in human cells.

Main Methods:

  • Integrated transcriptome-wide translational and structural analyses in Arabidopsis.
  • Deep learning modeling to identify and predict RNA structures downstream of uAUGs (uAUG-ds).
  • Comparative analysis of RNA helicase function in plants and human cells.

Main Results:

  • Transcripts with immune-induced translation are enriched with uORFs.
  • Hairpin structures (uAUG-ds) downstream of uAUGs mediate selective uAUG translation in non-infected conditions.
  • Induced RNA helicases resolve uAUG-ds structures upon immune challenge, enabling translation of defense proteins.
  • uAUG-ds mediated regulation is conserved in human cells.

Conclusions:

  • mRNA structures dynamically regulate translation start-codon selection.
  • uAUG-ds act as a general mechanism for translational reprogramming across kingdoms.
  • Dynamic remodeling of mRNA structures by RNA helicases is crucial for adaptive translation.