Translational Regulation of the JunD Messenger RNA
| Autor: | Curt M. Pfarr, Johnny D Short |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Untranslated region
Proto-Oncogene Proteins c-jun JUNB Molecular Sequence Data Biology Transfection Biochemistry Cell Line Mice Open Reading Frames Start codon Translational regulation Tumor Cells Cultured Protein biosynthesis Animals Humans Protein Isoforms RNA Messenger Phosphorylation Codon Luciferases Molecular Biology Messenger RNA Binding Sites Base Sequence Models Genetic Sequence Homology Amino Acid integumentary system Cell Biology Molecular biology Rats Internal ribosome entry site Open reading frame Gene Expression Regulation Protein Biosynthesis COS Cells Mutation Mutagenesis Site-Directed 5' Untranslated Regions Ribosomes HeLa Cells |
| Zdroj: | Journal of Biological Chemistry. 277:32697-32705 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m204553200 |
| Popis: | JunD, a member of the Jun family of nuclear transcription proteins, dimerizes with Fos family members or other Jun proteins (c-Jun or JunB) to form the activator protein 1 (AP-1) transcription factor. The junD gene contains no introns and generates a single mRNA. Here we show that two predominant JunD isoforms are generated by alternative initiation of translation, a 39-kDa full-length JunD protein (JunD-FL) by initiation at the first AUG codon downstream of the mRNA 5' cap and a shorter, 34-kDa JunD protein (DeltaJunD) by initiation at a second in-frame AUG codon. The JunD mRNA contains a long, G/C-rich 5'-untranslated region that is predicted to be highly structured and is important for regulating the ratio of JunD-FL and DeltaJunD protein expression. A third functional out-of-frame AUG directs translation from a short open reading frame positioned between the JunD-FL and DeltaJunD start sites. In addition, three non-AUG codons also support translation, an ACG codon (in-frame with JunD) and a CUG are positioned in the 5'-untranslated region, and a CUG codon (also in-frame with JunD) is located downstream of the short open reading frame. Mutation of these start sites individually had no affect on DeltaJunD protein levels, but mutation of multiple upstream start sites led to an increase in DeltaJunD protein levels, indicating that these codons can function cumulatively to suppress DeltaJunD translation. Finally, we show that the JunD mRNA does not possess an internal ribosome entry site and is translated in a cap-dependent manner. |
| Databáze: | OpenAIRE |
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