Purification and Properties of HuD, a Neuronal RNA-binding Protein

Chung, Sangmi; Lan, Jiang; Cheng, Simon K.; Furneaux, Henry

doi:10.1074/jbc.271.19.11518

Cited by 158 publications

(171 citation statements)

References 44 publications

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“…However, only the 36-kDa protein was cytoplasmic and therefore seemed the most likely one to be involved in mRNA polyadenylation in embryos. Members of the ELG family encode proteins that bind U-rich sequences in cytokine mRNAs similar to the eCPE and that range in size from 36 to 42 kDa (1,4,21,22). In Xenopus, several ELGs are expressed in the oocyte and early embryo (10).…”

Section: Resultsmentioning

confidence: 99%

“…Other members of the ELAV family, such as Hel-N1 (the human homolog of ElrB) and HuD (the human homolog of ElrD), are known to bind to AU-rich elements (4,6). To rule out the possibility that ElrA binds to Cl2 RNA simply because of its affinity to AU-rich sequences, we performed a gel retardation assay using the histone B4 3Ј UTR (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Members of this protein family do interact with the AUUUA degradation sequence (2,4,24). However, we should point out that the minimum number of uridine residues that can promote cytoplasmic polyadenylation in embryos is 12, which strongly correlates with the number of uridines required for binding of the 36-kDa protein/ElrA (34,35).…”

Section: Discussionmentioning

confidence: 99%

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The 36-Kilodalton Embryonic-Type Cytoplasmic Polyadenylation Element-Binding Protein in Xenopus laevis Is ElrA, a Member of the ELAV Family of RNA-Binding Proteins

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Richter

1997

Molecular and Cellular Biology

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The translational activation of several maternal mRNAs in Xenopus laevis is dependent on cytoplasmic poly(A) elongation. Messages harboring the UUUUUAU-type cytoplasmic polyadenylation element (CPE) in their 3 untranslated regions (UTRs) undergo polyadenylation and translation during oocyte maturation. This CPE is bound by the protein CPEB, which is essential for polyadenylation. mRNAs that have the poly(U) 12-27 embryonic-type CPE (eCPE) in their 3 UTRs undergo polyadenylation and translation during the early cleavage and blastula stages. A 36-kDa eCPE-binding protein in oocytes and embryos has been identified by UV cross-linking. We now report that this 36-kDa protein is ElrA, a member of the ELAV family of RNA-binding proteins. The proteins are identical in size, antibody directed against ElrA immunoprecipitates the 36-kDa protein, and the two proteins have the same RNA binding specificity in vitro. Cl2 and activin receptor mRNAs, both of which contain eCPEs, are detected in immunoprecipitated ElrA-mRNP complexes from eggs and embryos. In addition, this in vivo interaction requires the eCPE. Although a number of experiments failed to define a role for ElrA in cytoplasmic polyadenylation, the expression of a dominant negative ElrA protein in embryos results in an exogastrulation phenotype. The possible functions of ElrA in gastrulation are discussed.Early development in many animals is programmed by mRNAs inherited by the egg at the time of fertilization. While many of these mRNAs are translationally dormant in oocytes, they become activated in a sequence-specific manner at subsequent developmental periods. Several mechanisms are likely to control the translation of these messages, but one that has been studied extensively in Xenopus laevis is poly(A) elongation (31). Some mRNAs, which encode such proteins as c-Mos, cyclin B1, cyclin-dependent kinase 2 (Cdk2), and the earlydevelopment-specific histone B4, are polyadenylated and translated during oocyte maturation (27-29, 33, 39). Other mRNAs, however, undergo these processes sometime after fertilization; they encode such proteins as polypeptide chain release factor (Cl1), Cl2 (function unknown), and activin receptor (28,(34)(35)(36).Both groups of mRNAs contain two cis-acting elements located in their 3Ј untranslated regions (UTRs) that are required for cytoplasmic polyadenylation. One is the virtually ubiquitous hexanucleotide AAUAAA, which is also important for nuclear pre-mRNA cleavage and polyadenylation. The second, called the cytoplasmic polyadenylation element (CPE), is a U-rich sequence located upstream of the hexanucleotide. The exact sequence of CPE differs between the two groups of mRNAs mentioned. The maturation-type CPE is UUUUUAU (consensus), whereas the embryonic CPE (eCPE) is oligo (U) 12-27 (reviewed in reference 31). At least two mRNAs that are polyadenylated in embryos also contain a third cis-acting sequence in the 3Ј UTR: the masking element that prevents precocious polyadenylation during maturation (34, 35). Because deletion of the maskin...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The 36-Kilodalton Embryonic-Type Cytoplasmic Polyadenylation Element-Binding Protein in Xenopus laevis Is ElrA, a Member of the ELAV Family of RNA-Binding Proteins

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Richter

1997

Molecular and Cellular Biology

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“…3). Previous in vitro studies on Hu proteins have shown that RBDs 1 and 3 are required for binding to AREs and the poly(A) tail, respectively (Abe et al 1996b;Chung et al 1996;Ma et al 1997). Therefore, the binding of HuD to some speci®c ARE-containing mRNAs and also possibly the export of the mRNAs to the cytoplasm by shuttling may be involved in the induction of neurite outgrowth.…”

Section: The Novel Nes Of Hud and The Nucleocytoplasmic Shuttling Of mentioning

confidence: 99%

Cytoplasmic localization is required for the mammalian ELAV‐like protein HuD to induce neuronal differentiation

et al. 1999

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“…Likewise, hNT2 cells when induced to differentiate by retinoic acid exhibited a marked increase in the expression of human ELAV-like proteins which colocalized with mRNPs associated with polysomes (1). Hence, data from both of these studies support an important role for mammalian ELAV-like proteins in the processes of cell growth and differentiation.Interestingly, members of the ELAV family have been shown to bind the AU-rich regions of the 3ЈUTRs in cytokine and proto-oncogene mRNAs (5,14,27). In vitro binding studies with Hel-N1 documented preferential binding to the 3ЈUTRs of mRNAs which have short stretches of uridylate residues; however, in vivo RNA targets of ELAV proteins have not been identified (27).…”

mentioning

confidence: 99%

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

Jain

Andrews

McGowan

et al. 1997

Molecular and Cellular Biology

187

174

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3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3 untranslated regions (3 UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3 UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.Interaction of RNA-binding proteins with cis elements in mRNAs is believed to be involved in regulation of their stability and translational efficiency (reviewed in reference 32). The regulated stability of transferrin, granulocyte-macrophage colony-stimulating factor, and histone mRNAs has been shown, at least in part, to be controlled by the binding of specific proteins to consensus sequences in the 3Ј untranslated region (3ЈUTR) of these messages (3, 37, 41). Studies of tobacco mosaic virus, the Drosophila melanogaster developmental gene hunchback, human cytokine, and 15-lipoxygenase mRNAs have demonstrated that the 3ЈUTR also contains information capable of regulating translational efficiency which may be mediated by RNA-binding proteins (13,25,35,36). A major class of RNA-binding proteins which possess an 80-amino-acid consensus element, termed the RNA recognition motif (RRM) (39), which forms the core of a functional RNAbinding domain has been identified.Hel-N1 (human embryonic lethal abnormal vision [ELAV]-like neuronal protein 1), a mammalian homolog of Drosophila ELAV, is an mRNA-binding protein of the RRM family (15,16,27). Recent studies on Hel-N1, and the alternative form, Hel-N2 (lacking a 13-amino-acid segment between RRM2 and RRM3), in human medulloblastoma cells and embryonic carcinoma P19 cells have indicated that it plays a role in mRNA metabolism (15). These proteins are bound to poly(A) ϩ mRNA in granular RNP structures, and their expression is upregulated during neuronal cell differentiation of P19 cells (15). Likewise, hNT2 cells when induced to differentiate by retinoic acid exhibited a marked increase in the expression of human ELAV-like proteins which colocalized with mRNPs associated with polysomes (1). Hence, data from both of these studies support an important role for mammalian ELAV-like proteins in the processes of cell growth and differentiation.Interestingly, members of the ELAV family have been shown to bind the AU-rich regions of the 3ЈUTRs in cytokine and proto-oncogene m...

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Purification and Properties of HuD, a Neuronal RNA-binding Protein

Cited by 158 publications

References 44 publications

The 36-Kilodalton Embryonic-Type Cytoplasmic Polyadenylation Element-Binding Protein in Xenopus laevis Is ElrA, a Member of the ELAV Family of RNA-Binding Proteins

The 36-Kilodalton Embryonic-Type Cytoplasmic Polyadenylation Element-Binding Protein in Xenopus laevis Is ElrA, a Member of the ELAV Family of RNA-Binding Proteins

Cytoplasmic localization is required for the mammalian ELAV‐like protein HuD to induce neuronal differentiation

Ectopic Expression of Hel-N1, an RNA-Binding Protein, Increases Glucose Transporter (GLUT1) Expression in 3T3-L1 Adipocytes

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