Cited by 173RNA Research and SplicingRNA regulation and diseaseRNA and protein synthesis mechanisms

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Modulation of mRNA stability as a novel therapeutic approach

Eberhardt, Wolfgang, Doller, Anke, Akool, El-Sayed, Pfeilschifter, Josef·2007·Pharmacology & Therapeutics

DOI 10.1016/j.pharmthera.2007.01.002

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Abstract

During the last decade evidence has accumulated that modulation of mRNA stability plays a central role in cellular homeostasis, including cell differentiation, proliferation and adaptation to external stimuli. The functional relevance of posttranscriptional gene regulation is highlighted by many pathologies, wherein occurrence tightly correlates with a dysregulation in mRNA stability, including chronic inflammation, cardiovascular diseases and cancer. Most commonly, the cis-regulatory elements of mRNA decay are represented by the adenylate- and uridylate (AU)-rich elements (ARE) which are specifically bound by trans-acting RNA binding proteins, which finally determine whether mRNA decay is delayed or facilitated. Regulation of mRNA decay by RNA stabilizing and RNA destabilizing factors is furthermore controlled by different intrinsic and environmental stimuli. The modulation of mRNA binding proteins, therefore, illuminates a promising approach for the pharmacotherapy of those key pathologies mentioned above and characterized by a posttranscriptional dysregulation. Most promisingly, intracellular trafficking of many of the mRNA stability regulating factors is, in turn, regulated by some major signaling pathways, including the mitogen-activated protein kinase (MAPK) cascade, the AMP-activated kinase (AMPK) and the protein kinase (PK) C (PKC) family. In this review, we present timely examples of genes regulated by mRNA stability with a special focus on signaling pathways involved in the ARE-dependent mRNA decay. A better understanding of these processes may form the basis for the development of novel therapeutics to treat major human diseases.

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Authors: Eberhardt, W., Doller, A., Akool, E.-S., & Pfeilschifter, J.
Affiliations: Goethe University Frankfurt (DE)
Corresponding author: Eberhardt, Wolfgang
ORCID: Eberhardt, Wolfgang
Pfeilschifter, Josef
Venue: Pharmacology & Therapeutics
Publisher: Elsevier BV
Published: 2007-04
Volume: 114
Issue: 1
Pages: 56-73
ISSN: 0163-7258 (ISSN-L)
DOI: 10.1016/j.pharmthera.2007.01.002
OpenAlex: W2073507583
Cited by: 173
References: 224
Citations by year: 2026: 2 · 2025: 4 · 2024: 8 · 2023: 8 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 2 · 2018: 8 · 2017: 7 · 2016: 2 · 2015: 9 · 2014: 10 · 2013: 10 · 2012: 12
FWCI: 1.54
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Keywords: mRNA stability, post-transcriptional regulation, AU-rich elements, mRNA degradation, RNA-binding proteins, MAPK signaling, AMPK, protein kinase C, chronic inflammation, cardiovascular disease, cancer, therapeutic target
MeSH terms: Animals, Humans, RNA, Messenger, Signal Transduction, RNA Stability, Regulatory Elements, Transcriptional

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Modulation of mRNA stability as a novel therapeutic approach

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