Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators with opposite functions.
The cAMP-responsive-element modulator (CREM) gene encodes both antagonists (CREM alpha/beta/gamma) and an activator (CREM tau) of cAMP-responsive transcription by alternative splicing. In adult mouse brain a predominant 21-kDa protein, not corresponding to any previously characterized transcript, is detected with specific CREM antibodies. A developmental switch occurs in brain as expression changes at birth from CREM alpha/beta to the 21-kDa protein. We show that the 21-kDa protein corresponds to S-CREM (short CREM), a protein produced by the use of an internal AUG initiation codon in the CREM tau transcript. S-CREM shares with the other CREM proteins the basic DNA-binding and leucine-zipper dimerization domain. S-CREM functions as a transcriptional repressor of cAMP-induced transcription. Thus, two proteins with opposite functions are generated by alternative translation using two AUG codons within the same reading frame.
Delmas
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Laboratoire De Génétique Moléculaire des Eucaryotes, U184 Institut National de la Santé et de la Recherche Médicale, Faculté de Medecine, Strasbourg, France.
Laoide
B M
BM
Masquilier
D
D
de Groot
R P
RP
Foulkes
N S
NS
Sassone-Corsi
P
P
D000818:Animals; D001921:Brain / Q000502:physiology; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D003062:Codon; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000235:genetics*; D005809:Genes, Regulator; D005822:Genetic Vectors; D051379:Mice; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D012097:Repressor Proteins; D014158:Transcription, Genetic; D014162:Transfection
D003062:Codon; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D015500:Chloramphenicol O-Acetyltransferase