Post-transcriptional regulation of the peripheral myelin protein gene PMP22/gas3.
The peripheral myelin protein PMP22 gene has been described as a growth arrest-specific gene gas3 and has been identified as disease gene of various demyelinating neuropathies. The gene consists of two highly conserved alternative noncoding 5'-exons la (CD25) and 1b (SR13), respectively. Differential expression patterns of these transcripts in vivo and in vitro suggest a very complex mode of PMP22 gene regulation, which cannot be explained merely by transcriptional control. In fact, the PMP22 gene is regulated on different post-transcriptional levels. While reverse transcriptase polymerase chain 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 resting cells we observed a specific cell cycle-regulated degradation of both transcripts. We further prepared diverse PMP22/CAT fusion genes to study the influence of the alternative 5'UTRs on PMP22 translation. Transient transfection of NIH3T3-fibroblasts and rat Schwann cells demonstrated that the alternative 5'UTRs (CD25 and SR13) and the 3'UTR exert differential regulatory influences on the translation efficiency.
Bosse
F
F
Department of Neurology, Heinrich-Heine-University of Düsseldorf, Federal Republic of Germany. bosse@uni-duesseldorf.de
Brodbeck
J
J
Müller
H W
HW
D020413:3' Untranslated Regions / Q000235:genetics; D016475:3T3 Cells; D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D017931:DNA Primers; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000235:genetics*; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015375:Receptors, Interleukin-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000378:metabolism; D014162:Transfection / Q000235:genetics