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Published on: February 5, 2019
Alternative usage of initiation codons in mRNA encoding the cAMP-responsive-element modulator generates regulators
V Delmas1, B M Laoide, D Masquilier
1Laboratoire De Génétique Moléculaire des Eucaryotes, U184 Institut National de la Santé et de la Recherche Médicale, Faculté de Medecine, Strasbourg, France.
Summary
A novel short protein, S-CREM, is generated from the CREM tau transcript in the adult mouse brain. This short CREM protein acts as a repressor of cAMP-induced transcription.
Area of Science:
- Molecular Biology
- Neuroscience
- Gene Regulation
Background:
- The cAMP-responsive-element modulator (CREM) gene produces transcription factors via alternative splicing.
- CREM proteins can act as either activators or antagonists of cAMP-responsive transcription.
- A previously uncharacterized 21-kDa protein is detected in adult mouse brain using CREM antibodies.
Purpose of the Study:
- To identify the 21-kDa protein detected in the adult mouse brain.
- To investigate the functional role of this novel protein in cAMP-mediated gene regulation.
- To understand the developmental switch in CREM protein expression in the brain.
Main Methods:
- Western blot analysis using specific CREM antibodies.
- Identification of protein sequence and transcript origin.
- Functional assays for transcriptional activity.
Main Results:
- The 21-kDa protein was identified as S-CREM (short CREM).
- S-CREM is produced by translation initiation from an internal AUG codon within the CREM tau transcript.
- S-CREM functions as a transcriptional repressor of cAMP-induced transcription.
- A developmental switch from CREM alpha/beta to S-CREM expression occurs at birth in the mouse brain.
Conclusions:
- Alternative translation initiation generates CREM proteins with opposing functions (activator vs. repressor).
- S-CREM represents a novel functional variant of CREM, acting as a repressor.
- The study reveals a complex regulatory mechanism for cAMP-mediated transcription in the brain involving alternative splicing and translation.
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