Modulation of mRNA stability as a novel therapeutic approach

Eberhardt, Wolfgang; Doller, Anke; Akool, El-Sayed; Pfeilschifter, Josef

doi:10.1016/j.pharmthera.2007.01.002

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

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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Adenylate-uridylate-rich elements are involved in mRNA degradation, and degradation rate and translation life cycle can be adjusted by replacing adenylate-uridylate-rich sequences found in the 3′ UTR.
“Studies have shown that adenylate-uridylate-rich elements are involved in mRNA degradation. Degradation rate and translation life cycle can be adjusted by replacing adenylate-uridylate-rich sequences found in the 3′ UTR.137–139”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [139]

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Regulation of cytoplasmic mRNA decay
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Posttranslational Modification of the AU-Rich Element Binding Protein HuR by Protein Kinase Cδ Elicits Angiotensin II-Induced Stabilization and Nuclear Export of Cyclooxygenase 2 mRNA
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A synonymous polymorphism of the Tristetraprolin (TTP) gene, an AU-rich mRNA-binding protein, affects translation efficiency and response to Herceptin treatment in breast cancer patients
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Elevated hydrostatic pressure triggers release of OPA1 and cytochrome C, and induces apoptotic cell death in differentiated RGC-5 cells.
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GAPDH as a model non-canonical AU-rich RNA binding protein
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A Novel High Throughput Biochemical Assay to Evaluate the HuR Protein-RNA Complex Formation
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Glucocorticoid‐induced leucine zipper is downregulated in human alveolar macrophages upon T oll‐like receptor activation
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Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype
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High-constitutive HuR phosphorylation at Ser 318 by PKCδ propagates tumor relevant functions in colon carcinoma cells
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Role of the RNA-binding protein HuR in human renal cell carcinoma
Danilin, S., Sourbier, C., Thomas, L., Lindner, V., Rothhut, S., Dormoy, V., Helwig, J., Didier Jacqmin, D., Lang, H., & Massfelder, T. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq052 · Cited by 64 · see citing works
Tristetraprolin-dependent Post-transcriptional Regulation of Inflammatory Cytokine mRNA Expression by Apolipoprotein A-I
Yin, K., Deng, X., Mo, Z., Zhao, G., Jiang, J., Cui, L.-B., Tan, C.-Z., Wen, G., Fu, Y., & Tang, C. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202275 · Cited by 64 · see citing works
PLAB induction in fenretinide-induced apoptosis of ovarian cancer cells occurs via a ROS-dependent mechanism involving ER stress and JNK activation
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Networks controlling mRNA decay in the immune system
Schott, J., & Stoecklin, G. (2010) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.13 · Cited by 63 · see citing works
mRNA stability and cancer: an emerging link?
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hnRNPDL extensively regulates transcription and alternative splicing.
Li, R., Hou, J., Wei, Y., Luo, X.-T., Ye, Y.-L., & Zhang, Y. (2019) · Gene · doi:10.1016/j.gene.2018.11.026 · Cited by 49 · see citing works
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Post-transcriptional gene regulation by MAP kinases via AU-rich elements
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Advances of mRNA vaccine in tumor: a maze of opportunities and challenges
Yuan, Y., Gao, F., Chang, Y., Zhao, Q., & He, X. (2023) · Biomarker Research · doi:10.1186/s40364-023-00449-w · Cited by 58 · see citing works
Design, Assembly, Production, and Transfection of Synthetic Modified mRNA
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KSRP, many functions for a single protein
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The sweet side of RNA regulation: glyceraldehyde‐3‐phosphate dehydrogenase as a noncanonical RNA ‐binding protein
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Expression of vasopressin receptors in ACTH-independent macronodular bilateral adrenal hyperplasia causing Cushing's syndrome: molecular, immunohistochemical and pharmacological correlates
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FXR1 Is an IL-19-Responsive RNA-Binding Protein that Destabilizes Pro-inflammatory Transcripts in Vascular Smooth Muscle Cells
Herman, A. B., Vrakas, C. N., Ray, M., Kelemen, S. E., Sweredoski, M. J., Moradian, A., Haines, D. S., & Autieri, M. V. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.07.002 · Cited by 48 · see citing works
RNA-binding proteins as a point of convergence of the PI3K and p38 MAPK pathways
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RBP EIF2S2 Promotes Tumorigenesis and Progression by Regulating MYC-Mediated Inhibition via FHIT-Related Enhancers
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Aberrant activation of AMP‐activated protein kinase contributes to the abnormal distribution of HuR in amyotrophic lateral sclerosis
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Plasminogen Activator Inhibitor Type 2
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Activation of p38 signaling increases utrophin A expression in skeletal muscle via the RNA-binding protein KSRP and inhibition of AU-rich element-mediated mRNA decay: implications for novel DMD therapeutics
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Deletion of protein kinase Cδ in mice modulates stability of inflammatory genes and protects against cytokine-stimulated beta cell death in vitro and in vivo
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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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