The DOI matches its Crossref record; 221 of the 224 references it cites were found in a registry or an index.
Modulation of mRNA stability as a novel therapeutic approach
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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“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
Schoenberg, D. R., & Maquat, L. E. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3160 · Cited by 656
Barrett, L. W., Fletcher, S., & Wilton, S. D. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-0990-9 · Cited by 641
Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601
Regulation of the expression of inducible nitric oxide synthase
Pautz, A., Art, J., Hahn, S., Nowag, S., Voss, C., & Kleinert, H. (2010) · Nitric Oxide · doi:10.1016/j.niox.2010.04.007 · Cited by 549
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Metadata
- Authors
- Eberhardt, W., Doller, A., Akool, E.-S., & Pfeilschifter, J.
- Affiliations
- Goethe University Frankfurt (DE)
- Corresponding author
- Eberhardt, Wolfgang
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2007-04
- Volume
- 114
- Issue
- 1
- Pages
- 56-73
- ISSN
- 0163-7258 (ISSN-L)
- 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
- 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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