RNA-binding protein Rbfox2 establishes lipid gene programs through hierarchical control of transcription factors in the embryonic heart.

RBFOX2 loss in embryonic hearts modulates the cardiac lipidome, causing lipid droplet accumulation, and establishes lipid gene programs via transcription-factor control.

• Why it matters: RNA-binding proteins’ roles in metabolic gene regulation are unclear, especially how they set lipidome identity during heart development.
• What they did: Using multi-transcriptomic and lipidomics approaches, the study mapped RBFOX2 targets in embryonic hearts, identified SOX4 as a key TF target, and showed RBFOX2 binds the human SOX4 3' UTR to regulate mRNA stability.
• The result: SOX4 drives lipid gene programs by binding promoters of lipid enzymes/regulators, and restoring SOX4 rescues lipid gene expression defects after RBFOX2 loss, linking RBFOX2–SOX4 to developing-heart lipidome identity.

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