Back

CRISPR epi-editing reveals regulatory crosstalk between alternative promoters and splicing in Neurexin isoform expression

Hsiao, Y. Y.; Gomez, A. M.

2025-09-13 molecular biology
10.1101/2025.09.10.675405 bioRxiv
Show abstract

The use of alternative promoters and splicing increases molecular complexity and diversifies cellular functions. However, mechanisms of crosstalk between transcription and splicing remain poorly understood. Here, we utilize CRISPR epi-editing in neurons to manipulate isoforms of the synaptic organizer, Neurexin-1, and elucidate mechanisms underlying the co-regulation of alternative promoters and splicing. Surprisingly, silencing individual Neurexin-1 promoters altered downstream promoter activity via transcriptional interference and biased splicing decisions. Our data reveals transcriptional interference as key to shaping cell type-specific Neurexin-1 isoforms in the mouse hippocampus and demonstrates the power of epi-editing to uncover regulatory interactions between RNA processes in the brain.

Matching journals

The top 2 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.