Differential mRNA splicing and precursor processing of neurokinin B in neuroendocrine tissues.

The tachykinin neurokinin B which is encoded on the tachykinin 3 precursor, has prominent roles in both neuronal and endocrine systems, yet little is known about its evolution, potential splice variants and the manner in which it is processed. Here, we deduce the diversity within the vertebrate tachykinin 3 precursors, and identify novel tachykinin 3 splice variants and precursors. A total of 35 different tachykinin 3 precursors were identified in mammals, birds and reptiles. Nine additional alternatively spliced tachykinin 3 mRNA transcripts were also discovered in humans leading to the formation of three tachykinin 3 precursors (named alpha, beta and gamma tachykinin 3), but no novel tachykinin. gamma tachykinin 3, albeit rarer, was not found to encode neurokinin B. Differential processing of the tachykinin 3 precursor in the human placenta leads to the formation of potential NH2-terminally extended forms of neurokinin B. Moreover, we found increased proteolytic cleavage of the tachykinin 3 precursor during the pregnancy syndrome of pre-eclampsia. We have established neurokinin B to be an evolutionarily conserved peptide, nonetheless the significance of the three different tachykinin 3 precursors is not clear, but could represent an evolutionarily redundant splicing mechanism once employed by an ancestral gene that encoded two tachykinins. Our results indicate that differential mRNA splicing and precursor processing is likely to play an important role in differentiating the actions of the tachykinin 3 gene products in both neuronal and endocrine tissues.