An mRNA Stability Complex Functions with Poly(A)-Binding Protein To Stabilize mRNA In Vitro
Open accessAbstract
The stable globin mRNAs provide an ideal system for studying the mechanism governing mammalian mRNA turnover. alpha-Globin mRNA stability is dictated by sequences in the 3' untranslated region (3'UTR) which form a specific ribonucleoprotein complex (alpha-complex) whose presence correlates with mRNA stability. One of the major protein components within this complex is a family of two polycytidylate-binding proteins, alphaCP1 and alphaCP2. Using an in vitro-transcribed and polyadenylated alpha-globin 3'UTR, we have devised an in vitro mRNA decay assay which reproduces the alpha-complex-dependent mRNA stability observed in cells. Incubation of the RNA with erythroleukemia K562 cytosolic extract results in deadenylation with distinct intermediates containing a periodicity of approximately 30 nucleotides, which is consistent with the binding of poly(A)-binding protein (PABP) monomers. Disruption of the alpha-complex by sequestration of alphaCP1 and alphaCP2 enhances deadenylation and decay of the mRNA, while reconstitution of the alpha-complex stabilizes the mRNA. Similarly, PABP is also essential for the stability of mRNA in vitro, since rapid deadenylation resulted upon its depletion. An RNA-dependent interaction between alphaCP1 and alphaCP2 with PABP suggests that the alpha-complex can directly interact with PABP. Therefore, the alpha-complex is an mRNA stability complex in vitro which could function at least in part by interacting with PABP.
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The poly(A) tail regulates the fate of mRNA by synergy with the 5' cap, the internal ribosomal entry site, and various RNA stability determinants.
“The poly(A) tail regulates the fate of mRNA by synergy with the 5Ј cap, with the internal ribosomal entry site, and with various RNA stability determinants.31,[38][39][40][41]”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [40]
The Discussion (page not available in our copy) describes an interaction between a stability complex on the α-globin mRNA 3′ UTR and poly(A)-binding protein that may slow deadenylation. The paper also discusses protective roles for the 5′ cap and poly(A) tail, but the passages do not establish synergy between them or address synergy with an internal ribosomal entry site. (LLM, conf=0.86)
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- Authors
- Wang, Z., Day, N., Trifillis, P., & Kiledjian, M.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-07-01
- Volume
- 19
- Issue
- 7
- Pages
- 4552-4560
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84253
- OpenAlex
- W1838293083
- Cited by
- 262
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 6 · 2022: 18 · 2021: 4 · 2020: 4 · 2019: 9 · 2018: 5 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 8 · 2013: 3 · 2012: 12
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK051611, DK 51611)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- mRNA stability, poly(A)-binding protein, alpha-globin mRNA, 3' untranslated region, alpha complex, mRNA degradation, deadenylation, ribonucleoprotein complexes, mRNA turnover
- MeSH terms
- Animals, Cattle, DNA-Binding Proteins, Globins, HeLa Cells, Humans, RNA, Messenger, Transcription Factors, RNA-Binding Proteins, K562 Cells, 3' Untranslated Regions, Heterogeneous-Nuclear Ribonucleoproteins, Poly(A)-Binding Proteins
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