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Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators with opposite functions.

V Delmas·B M Laoide·D Masquilier·R P de Groot·N S Foulkes·P Sassone-Corsi
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Abstract

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.

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AnimalsBrainCell LineChloramphenicol O-AcetyltransferaseChromosome DeletionCodonCyclic AMP Response Element ModulatorDNA-Binding ProteinsGenes, RegulatorGenetic VectorsMiceRNA SplicingRNA, MessengerRepressor ProteinsTranscription, GeneticTransfectionJournal ArticleResearch Support, Non-U.S. Gov't

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V Delmas, B M Laoide, D Masquilier, R P de Groot, N S Foulkes, P Sassone-Corsi. 1992-05-15. Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators with opposite functions.. https://doi.org/10.1073/pnas.89.10.4226

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