Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human β-Globin mRNA
Open accessAbstract
Human globins are encoded by mRNAs exhibiting high stabilities in transcriptionally silenced erythrocyte progenitors. Unlike alpha-globin mRNA, whose stability is enhanced by assembly of a specific messenger RNP (mRNP) alpha complex on its 3' untranslated region (UTR), neither the structure(s) nor the mechanism(s) that effects the high-level stability of human beta-globin mRNA has been identified. The present work describes an mRNP complex assembling on the 3' UTR of the beta-globin mRNA that exhibits many of the properties of the stability-enhancing alpha complex. The beta-globin mRNP complex is shown to contain one or more factors homologous to alphaCP, a 39-kDa RNA-binding protein that is integral to alpha-complex assembly. Sequence analysis implicates a specific 14-nucleotide pyrimidine-rich track within its 3' UTR as the site of beta-globin mRNP assembly. The importance of this track to mRNA stability is subsequently verified in vivo using mice expressing human beta-globin transgenes that contain informative mutations in this region. In combination, the in vitro and in vivo analyses indicate that the high stabilities of the alpha- and beta-globin mRNAs are maintained through related mRNP complexes that may share a common regulatory pathway.
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Sequence elements within the 3' and 5' noncoding regions of RNA have been characterized as important factors in regulating transcript stability, in ways that are not completely understood.
“Sequence elements within the 3Ј and 5Ј noncoding regions of the RNA molecule have been characterized as important factors in regulating the stability of a transcript in ways that are not completely understood.32,33”
From Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells (2006) · cites this paper as [33]
The paper’s introductory discussion says that cis-acting elements, usually in the 3′ UTR, regulate mRNA stability; the Discussion identifies a stability element in the β-globin 3′ UTR. It also describes the 5′ cap as a general stabilizing feature, but does not characterize sequence elements within the 5′ noncoding region as stability regulators. Page numbers are not provided in our copy. (LLM, conf=0.86)
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- Authors
- Yu, J., & Russell, J. E.
- Affiliations
- University of Pennsylvania (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2001-09
- Volume
- 21
- Issue
- 17
- Pages
- 5879-5888
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC87307
- OpenAlex
- W2100018747
- Cited by
- 90
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R29HL056038, HL 56038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- beta-globin mRNA, mRNA stability, 3' untranslated region, alpha-globin mRNA, RNA-binding proteins, transgenic mice, translational regulation
- MeSH terms
- Animals, Base Sequence, Globins, Humans, Mice, Transgenic, Molecular Sequence Data, Nucleic Acid Conformation, Ribonucleoproteins, Structure-Activity Relationship, 3' Untranslated Regions, RNA Stability, Mice
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