A candidate HNRNPU-CHD2 RNA-processing axis in neurodevelopmental disease

HNRNPU knockdown in HEK293T cells links HNRNPU dosage to CHD2 splicing, with 107 reproducible HNRNPU peaks across CHD2 and a frameshift-prone exon switch.

• Why it matters: The programs connecting HNRNPU haploinsufficiency to neuronal dysfunction are unclear, limiting how HNRNPU-related neurodevelopmental disease mechanisms can be mapped.
• What they did: In HEK293T cells, HNRNPU depletion followed by gene-expression and alternative-splicing profiling identified 1,222 genes altered at both levels, including CHD2; K562 eCLIP found 107 HNRNPU peaks across CHD2.
• The result: Regulated CHD2 exons introduce a reading-frame shift with premature termination codons predicting nonsense-mediated decay, and CHD2 depletion in SH-SY5Y shifts cell-cycle, DNA-repair, and neural gene programs.

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