Translation start site multiplicity of the CCAAT/enhancer binding protein α mRNA is dictated by a small 5′ open reading frame

The CCAAT/enhancer binding proteins (C/EBP) α and β of the bZIP family of transcription factors each occur as multiple forms due to translation Initiation at different in-frame AUG codons from the same messenger RNA. The C/EBPα mRNAs of chicken, rat and Xenopus all contain a small 5' open readi...

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Bibliographic Details
Published in:Nucleic acids research 1994, Vol.22 (25), p.5540-5547
Main Authors: Calkhoven, Cor F., Bouwman, Peter R.J., Snippe, Lenie, AB, Geert
Format: Article
Language:English
Subjects:
Animals
Base Sequence
CCAAT-Enhancer-Binding Proteins
Chickens
DNA Primers - chemistry
DNA-Binding Proteins - genetics
In Vitro Techniques
Molecular Sequence Data
Nuclear Proteins - genetics
Open Reading Frames
Protein Biosynthesis
RNA, Messenger - metabolism
Structure-Activity Relationship
Transcriptional Activation
xenopus
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Summary:The CCAAT/enhancer binding proteins (C/EBP) α and β of the bZIP family of transcription factors each occur as multiple forms due to translation Initiation at different in-frame AUG codons from the same messenger RNA. The C/EBPα mRNAs of chicken, rat and Xenopus all contain a small 5' open reading frame (5'ORF) whose size (18 nucleotldes) and distance (seven nucleotides) to the C/EBPα clstron has been conserved in vertebrate evolution. The present studies shows that the small 5'ORF Is crucial to the leaky scanning mechanism of ribosomes causing a fraction of them to ignore the first C/EBPα AUG codon and to start at Internal AUGs. Our data challenge the view that translational start site multiplicity is mainly governed by the sequence context of the potential initiation codons. Western analysis showed that the two major chicken C/EBPα translation products, the full-length cC/EBPα-42 which acts a frans-actlvator in liver and the N-terminally truncated cC/EBPα-29 which lacks transcription activation potential, occur In a fixed ratio which Is similar In different expressing tissues, like liver, lung and small intestine. The presence of a similar, thusfar unnoticed, small ORF 5′ to the major initiation codon of C/EBPβ mRNA suggests that start site multiplicity from this mRNA may be governed by the same mechanism.
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/22.25.5540