p21waf1 mRNA Contains a Conserved Element in Its 3′-Untranslated Region That Is Bound by the Elav-like mRNA-stabilizing Proteins
Open accessAbstract
The Elav-like proteins are specific mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family (HuD, HuC, and Hel-N1) are required for neuronal differentiation. In this report, using purified HuD protein we have localized a high affinity HuD binding site to a 42-nucleotide region within a U-rich tract in the 3'-untranslated region p21(waf1) mRNA. The binding of HuD to this site is readily displaced by an RNA oligonucleotide encoding the HuD binding site of c-fos. The sequence of this binding site is well conserved in human, mouse, and rat p21(waf1) mRNA. p21(waf1) is an inhibitor of cyclin-dependent kinases and proliferating cell nuclear antigen and induces cell cycle arrest at G1/S, a requisite early step in cell differentiation. The identification of an Elav-like protein binding site in the 3'-untranslated region of p21(waf1) provides a novel link between the induction of differentiation, mRNA stability, and the termination of the cell cycle.
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HuD binds and regulates several mRNAs encoding proteins with important functions in neuronal differentiation, including cell cycle arrest (p21cip1/waf1), neuroblast proliferation (MSI-1), neuron migration (MARCKS), neurite extension (GAP-43, Tau, AChE), synapse formation (NOVA-1), and neuronal growth and survival (NGF, BDNF, NT-3).
“In addition to these transcripts, HuD has been shown to bind and regulate several other mRNAs in vitro and in vivo, many of which encode proteins with important functions in neuronal differentiation such as cell cycle arrest (p21cip1/waf1) (Joseph et al. 1998), neuroblast proliferation (MSI-1) (Ratti et al. 2006), neuron migration (MARCKS) (Wein et al. 2003), neurite extension ([GAP-43] [Chung et”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Joseph et al. 1998
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- Authors
- Joseph, B., Orlian, M., & Furneaux, H.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Furneaux, Henry
- ORCID
- Furneaux, Henry
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 273
- Issue
- 32
- Pages
- 20511-20516
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1988425964
- Cited by
- 127
- References
- 4
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 2 · 2018: 1 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 7
- FWCI
- 2.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P30-CA-08748, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- p21, 3' untranslated region, ELAV-like proteins, HUD, mRNA-binding proteins, mRNA stability, conserved binding sites, c-fos, cell cycle arrest, G1/S cell cycle arrest, cell differentiation, cyclin-dependent kinases, proliferating cell nuclear antigen
- MeSH terms
- ELAV-Like Protein 4, Animals, Base Sequence, Binding Sites, Binding, Competitive, Cell Cycle, Cell Differentiation, Enzyme Inhibitors, Humans, Molecular Sequence Data, Nerve Tissue Proteins, Oligonucleotides, Ribonucleases, Ribonucleoproteins, RNA, Messenger, Cyclins, RNA-Binding Proteins, Genes, fos, Conserved Sequence, Cyclin-Dependent Kinases, Cyclin-Dependent Kinase Inhibitor p21, Mice, Rats, ELAV Proteins
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