Aberrant recursive splicing in a human disease locus.

A deletion of a recursive splice site in CADM2 reduces gene expression and alters neuronal gene regulation, linking RS to neuropsychiatric traits in humans and rodents.

• Why it matters: Understanding how noncoding regulatory mechanisms like recursive splicing influence gene expression is crucial for elucidating genetic contributions to neuropsychiatric disorders, which remain poorly understood.
• What they did: Using CRISPR, the study modeled intronic deletions removing RS1 in CADM2 in human neurons and rodents, examining effects on RNA abundance, gene expression, and behavior.
• The result: Loss of RS1 decreased CADM2 expression and disrupted neuronal gene regulation, with rodent models showing modest behavioral and brain connectivity changes, highlighting RS as a regulatory mechanism in neuropsychiatric traits.