Post-transcriptional regulation of the peripheral myelin protein gene PMP22/Gas3

The peripheral myelin protein PMP22 gene has been described as a growth arr est-specific gene gas3 and has been identified as disease gene of various d emyelinating neuropathies. The gene consists of two highly conserved altern ative noncoding 5'-exons 1a (CD25) and 1b (SR13), respectively. Differentia l expression patterns of these transcripts in vivo and in vitro suggest a v ery complex mode of PMP22 gene regulation, which cannot be explained merely by transcriptional control, In fact, the PMP22 gene is regulated on differ ent post-transcriptional levels. While reverse transcriptase polymerase cha in reaction (RT-PCR) analyses revealed no alterations in stability for both PMP22 transcripts in randomly growing Schwann cell cultures of rat sciatic nerve for at least 8 hours, in serum-induced synchronized cultures of rest ing cells we observed a specific cell cycle-regulated degradation of both t ranscripts. We further prepared diverse PMP22/CAT fusion genes to study the influence of the alternative 5'UTRs on PMP22 translation. Transient transf ection of NIH3T3-fibroblasts and rat Schwann cells demonstrated that the al ternative 5'UTRs: (CD25 and SR13) and the 3'UTR exert differential regulato ry influences on the translation efficiency. J. Neurosci. Res. 55:164-177, 1999. (C) 1999 Wiley-Liss, Inc.