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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
Signaling to translational control pathways: diversity in gene regulation in inflammatory and vascular cells
Stephan W Lindemann1, Andrew S Weyrich, Guy A Zimmerman
1Department of Internal Medicine and the Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Abstract:
The expression of a subset of genes is strongly controlled at translational checkpoints, a major mechanism of posttranscriptional regulation. Inflammatory and vascular cells receive outside-in signals to specialized pathways that regulate translation of specific messenger RNAs in a transcript-specific fashion and thereby influence key features of cellular phenotype. These pathways and the expression of proteins that they control may be dysregulated in cardiovascular diseases and are therapeutic targets.
Insights
Gene expression is regulated by translational checkpoints, a key posttranscriptional mechanism. These pathways control cellular function and may be targeted for cardiovascular disease therapies.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Gene expression is tightly regulated at multiple levels.
- Posttranscriptional regulation, particularly at the translational level, plays a critical role in controlling protein synthesis.
- Specific signaling pathways modulate translation of messenger RNAs (mRNAs) in response to cellular stimuli.
Purpose of the Study:
- To investigate the role of translational checkpoints in regulating gene expression.
- To understand how these pathways influence cellular phenotype in inflammatory and vascular cells.
- To identify these regulatory pathways as potential therapeutic targets for cardiovascular diseases.
Main Methods:
- Analysis of gene expression patterns.
- Study of signaling pathways involved in mRNA translation.
- Investigation of transcript-specific regulation of protein synthesis.
- Examination of cellular responses in inflammatory and vascular cells.
Main Results:
- A subset of genes is significantly controlled at the translational level.
- Outside-in signals activate specialized pathways that regulate translation of specific mRNAs.
- These pathways influence key aspects of cellular phenotype.
Conclusions:
- Translational checkpoints are a major mechanism of posttranscriptional gene regulation.
- Dysregulation of these pathways and their protein targets is implicated in cardiovascular diseases.
- Targeting these pathways offers a promising therapeutic strategy for cardiovascular conditions.
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