Trans-splicing of a voltage-gated sodium channel is regulated by nerve growth factor.

Mammalian sensory neurons express a voltage-gated sodium channel named SNS. Here we report the identification of an SNS transcript (SNS-A) that contains an exact repeat of exons 12, 13 and 14 encoding a partial repeat of domain II. Because the exons 12-14 are present in single copies in genomic DNA, the SNS-A transcript must arise by trans-splicing. Nerve growth factor, which regulates pain thresholds, and the functional expression of voltage-gated sodium channels increases the levels of the SNS-A transcript several-fold both in vivo and in vitro as measured by RNase protection methods, as well as RT-PCR. These data demonstrate a novel regulatory role for the nerve growth factor and are the first example of trans-splicing in the vertebrate nervous system.