ALS-linked FUS mutation impairs GEMIN5-dependent mRNA recruitment to neuronal late endosomes.

GEMIN5-dependent recruitment of endosome-associated mRNAs to RAB7A-positive late endosomes is impaired by an ALS-linked FUS mutation in human motor neurons.

• Why it matters: Neurons require precise long-distance mRNA positioning, but how specific transcripts are selectively loaded onto endosomal carriers is unclear, especially in ALS-linked conditions.
• What they did: Using APEX2-mediated proximity labeling, the external transcriptome of RAB7A-positive endosomes was mapped, revealing mRNAs enriched for endosomal, axonal, and synaptic functions with conserved 5'UTRs that GEMIN5 binds to promote recruitment.
• The result: ALS-associated conditions show a conspicuous loss of endosome-associated transcripts and mislocalization of GEMIN5 from endosomes, highlighting endosomal mRNA loading as a vulnerable neuronal homeostasis axis.

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