Abstract
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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence
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Binding Sites / genetics
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Binding, Competitive
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Cell Cycle / physiology
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Cell Differentiation / physiology
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Conserved Sequence / genetics
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclins / genetics*
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ELAV Proteins
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ELAV-Like Protein 4
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Enzyme Inhibitors / pharmacology
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Genes, fos / genetics
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Humans
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Mice
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Molecular Sequence Data
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Nerve Tissue Proteins*
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Oligonucleotides / metabolism
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RNA, Messenger / chemistry*
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RNA-Binding Proteins / physiology*
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Rats
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Ribonucleases / metabolism
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Ribonucleoproteins / physiology*
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cdkn1a protein, rat
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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ELAV Proteins
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ELAV-Like Protein 4
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ELAVL4 protein, human
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Elavl4 protein, mouse
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Enzyme Inhibitors
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Nerve Tissue Proteins
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Oligonucleotides
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RNA, Messenger
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RNA-Binding Proteins
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Ribonucleoproteins
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Cyclin-Dependent Kinases
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Ribonucleases