Detection and Characterization of a 3′ Untranslated Region Ribonucleoprotein Complex Associated with Human α-Globin mRNA Stability
Open accessAbstract
The highly stable nature of globin mRNA is of central importance to erythroid cell differentiation. We have previously identified cytidine-rich (C-rich) segments in the human alpha-globin mRNA 3' untranslated region (alpha-3'UTR) which are critical in the maintenance of mRNA stability in transfected erythroid cells. In the present studies, we have detected trans-acting factors which interact with these cis elements to mediate this stabilizing function. A sequence-specific ribonucleoprotein (RNP) complex is assembled after incubation of the alpha-3'UTR with a variety of cytosolic extracts. This so-called alpha-complex is sequence specific and is not formed on the 3'UTR of either beta-globin or growth hormone mRNAs. Furthermore, base substitutions within the C-rich stretches which destabilize alpha-globin mRNA in vivo result in a parallel disruption of the alpha-complex in vitro. Competition studies with a series of homoribopolymers reveals a striking sensitivity of alpha-complex formation to poly(C), suggesting the presence of a poly(C)-binding activity within the alpha-complex. Three predominant proteins are isolated by alpha-3'UTR affinity chromatography. One of these binds directly to poly(C). This cytosolic poly(C)-binding protein is distinct from previously described nuclear poly(C)-binding heterogeneous nuclear RNPs and is necessary but not sufficient for alpha-complex formation. These data suggest that a messenger RNP complex formed by interaction of defined segments within the alpha-3'UTR with a limited number of cytosolic proteins, including a potentially novel poly(C)-binding protein, is of functional importance in establishing high-level stability of alpha-globin mRNA.
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- Authors
- Wang, X., Kiledjian, M., Weiss, I. M., & Liebhaber, S. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1995-03-01
- Volume
- 15
- Issue
- 3
- Pages
- 1769-1777
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC230401
- OpenAlex
- W2114130204
- Cited by
- 192
- References
- 64
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 3 · 2014: 2 · 2013: 6 · 2012: 4
- FWCI
- 4.77
- 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
- Howard Hughes Medical Institute
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P60HL038632)
- 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
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- alpha-globin mRNA, mRNA stability, 3' untranslated region, ribonucleoprotein complexes, trans-acting factors, poly(C), erythroid differentiation, mRNA-binding proteins, globin mRNA
- MeSH terms
- Animals, Base Sequence, Cell Line, Cell Nucleus, Chromatography, Affinity, Leukemia, Erythroblastic, Acute, Fibroblasts, Globins, Humans, Molecular Sequence Data, Poly C, Ribonucleoproteins, RNA, Messenger, Growth Hormone, Templates, Genetic, Transfection, Protein Biosynthesis, Oligonucleotide Probes, Polymerase Chain Reaction, Mutagenesis, Site-Directed, RNA-Binding Proteins, Point Mutation, DNA Primers, Mice
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