ERV-derived dsRNAs induce stress granules that drive neural crest fate to initiate melanoma

ERV-derived dsRNAs trigger eif2ak2-dependent stress granules in zebrafish precursor lesions, and G3BP1/2 activity is linked to accelerated melanoma onset.

• Why it matters: The switch that reprograms oncogenic melanocytes into neural crest-like melanoma cells is unclear, limiting targeted prevention and early intervention.
• What they did: In zebrafish, stage-specific ERV elements (zferv before crestin) generate dsRNA that induces stress granules; G3BP1 overexpression accelerates onset, while mosaic melanocyte-specific g3bp1/2 knockout delays it, and G3BP1/2 inhibition removes precursor lesions.
• The result: In human nevi and melanomas, analogous ERV programs assemble stress granules that sequester and translationally repress SOX10-regulating mRNAs, including KMT2D, and kmt2d mosaic knockout enhances SOX10-driven neural crest reactivation.

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