EXPRESSION OF POLYADENYLATED AND NONPOLYADENYLATED TRKC TRANSCRIPTS IN THE RODENT CENTRAL-NERVOUS-SYSTEM

We have previously isolated a full-length cDNA clone encoding rat TrkC, a member of the Trk family of tyrosine kinase receptors, that specifically mediates biological responses to neurotrophin-3. Here, we report the identification of five major trkC transcripts in the adult and developing rat and mouse brain suggesting the presence of several TrkC receptors. Northern blot hybridizations revealed that three of these trkC transcripts (of 14, 3.9 and 4.8 kb) were poly(A)(+) messenger RNAs, while the two others, of shorter size (1.1 and 0.7 kb), were poly(A)(-) messenger RNAs. All transcripts were expressed in 11 brain regions but poly(A)(-) messenger RNAs were found at much higher levels than poly(A)(+) messenger RNAs in the cerebellum. Hybridization with five oligonucleotide and two complementary DNA probes, corresponding to different parts of the full-length trkC complementary DNA, revealed that the two poly(A)(-) transcripts may encode for receptors truncated in their extracellular and kinase intracellular domains. During ontogeny, poly(A)(-) trkC messenger RNAs were found at low amounts al prenatal and early postnatal ages with a drastic increase in the cerebellum at postnatal day 30. No poly(A)(-) transcript was identified for the trkB gene. In situ hybridization revealed that trkC messenger RNAs are expressed both in granular and Purkinje cells in the cerebellum. Northern blot on RNA extracted from mice mutant strains with degeneration of either granular or both granular and Purkinje cells suggested that poly(A)(-) and poly(A)(+) trkC messenger RNAs are expressed within the same cells. We have demonstrated the existence of several trkC transcripts that differ both by their size and polyadenylation. This phenomenon could be of physiological relevance in regulating TrkC functions. To the best of our knowledge, this is an original feature for a mammalian gene expression. Studies focused on poly(A)(-) messenger RNAs could give rise to the identification of other genes expressed in a similar fashion.