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Updated: Jun 28, 2026

Assessment of Selective mRNA Translation in Mammalian Cells by Polysome Profiling
Published on: October 28, 2014
Regulating amyloid precursor protein synthesis through an internal ribosomal entry site
Monique E Beaudoin1, Vincent-Joseph Poirel, Leslie A Krushel
1Department of Biochemistry, Neurosciences Program, University of Colorado Denver School of Medicine, Aurora, CO 80045, USA.
Alzheimer's disease (AD) involves amyloid precursor protein (APP). This study reveals APP mRNA uses an internal ribosome entry site (IRES) for translation, a process influenced by iron and ischemia, both linked to AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Amyloid precursor protein (APP) expression is central to Alzheimer's disease (AD) pathogenesis.
- Targeting APP expression at transcriptional, translational, or protein stability levels is a potential therapeutic strategy.
- The translational regulation of APP mRNA remains largely uncharacterized.
Purpose of the Study:
- To investigate the mechanism of endogenous APP mRNA translation.
- To identify regulatory elements and conditions influencing APP translation.
- To explore the role of internal ribosome entry site (IRES)-mediated translation in APP synthesis.
Main Methods:
- Utilized neural cell lines to study endogenous APP mRNA translation.
- Mapped the functional domain of the identified APP IRES.
- Assessed the impact of increased intracellular iron concentration and ischemia on APP IRES activity.
- Investigated the dependence of IRES enhancement on de novo transcription.
Main Results:
- Endogenous APP mRNA is translated in neural cells via an IRES in its 5'-untranslated leader.
- The active IRES region is localized within the first 50 nucleotides of the 5'-leader.
- APP IRES activity is enhanced by conditions associated with AD: increased intracellular iron and ischemia.
- This enhancement of APP IRES activity requires de novo transcription.
Conclusions:
- Internal initiation of translation via an IRES is a significant mechanism for APP synthesis.
- APP IRES activity is modulated by cellular conditions relevant to Alzheimer's disease.
- This translational control mechanism offers a novel target for AD therapeutic strategies.
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Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life

