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 contai ns an exact repeat of exons 12, 13 and 14 encoding a partial repeat of doma in 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, wh ich regulates pain thresholds, and the functional expression of voltage-gat ed sodium channels increases the levels of the SNS-A transcript several-fol d both in vivo and in vitro as measured by RNase protection methods, as wel l as RT-PCR, These data demonstrate a novel regulatory role for the nerve g rowth factor and are the first example of trans-splicing in the vertebrate nervous system. (C) 1999 Federation of European Biochemical Societies.