Physiological mapping and prediction reveal stress-responsive translation initiation landscapes

TISCA2 maps eIF5B-associated translation initiation sites genome-wide and shows arsenite-induced integrated stress response shifts start-site usage toward downstream initiation.

• Why it matters: Translation initiation output is dynamic, yet physiological start-site landscapes in cells and tissues are not well resolved, especially for short or overlapping translons.
• What they did: TISCA2 is an inhibitor-free approach that captures initiating ribosomes via eIF5B to identify start sites directly; it is validated with N-terminal proteomics and HLA-I immunopeptidomics.
• The result: IncepTIS predicts position-resolved, condition-dependent initiation landscapes and, when used for optimization, generates de novo mRNA 5' leaders with stress-responsive initiation patterns.

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