Zebrafish CTH1, a C3H zinc finger protein, is expressed in ovarian oocytes and embryos

Kronnie, Geertruy te; Stroband, H.W.J.; Schipper, H.; Samallo, J.

doi:10.1007/s004270050276

Cited by 17 publications

(7 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 for recent review). In mammals, there are three known members of this protein family, whereas fish and frogs express a fourth member that seems to consist of a group of closely related proteins (2)(3)(4). The characteristic tandem zinc finger domain of these proteins consists of two zinc fingers with 18 amino acids between fingers, strict intrafinger spacing of Cx8Cx5Cx3H, and a characteristic sequence motif leading into each finger of R(K)YKTEL or a closely related variant.…”

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

Characteristics of the Interaction of a Synthetic Human Tristetraprolin Tandem Zinc Finger Peptide with AU-rich Element-containing RNA Substrates

Blackshear

Lai²,

Kennington³

et al. 2003

Journal of Biological Chemistry

116

130

View full text Add to dashboard Cite

Tristetraprolin (TTP) and its two known mammalian family members are tandem CCCH zinc finger proteins that can bind to AU-rich elements (AREs) in cellular mRNAs and destabilize those transcripts, apparently by initiating their deadenylation. Previous studies have shown that the ϳ70-amino acid tandem zinc finger domain of TTP is required and sufficient for RNA binding, and that the integrity of both zinc fingers is also required. However, little is known about the kinetics or structure of the peptide-RNA interaction, in part because of difficulties in obtaining soluble recombinant protein or peptides. We characterized the binding of a synthetic 73-amino acid peptide from human TTP to the tumor necrosis factor (TNF) ARE by gel mobility shift analyses and fluorescence anisotropy experiments. Both types of studies yielded a peptide-RNA dissociation constant of ϳ10 nM. Surprisingly, we found that the "footprint" from the TNF ARE required for peptide binding was only ϳ9 bases and that two molecules of peptide could bind to probes containing as little as 19 bases. An identical recombinant peptide exhibited gel shift characteristics similar to those of the synthetic peptide. NMR analysis of the 15 N-labeled recombinant peptide suggested that its first zinc finger was structured in solution but that the second was not. The titration of oligonucleotides representing 17, 13, and even 9 bases of the TNF ARE caused an essentially identical, dramatic shift of existing resonances, and the appearance of new resonances in the peptide spectra, so that all amino acids could be assigned. These data suggest that this TTP peptide-RNA complex is structured in solution and might be amenable to NMR structure determination. Tristetraprolin (TTP)1 is the prototype of a small family of eukaryotic CCCH tandem zinc finger proteins (see Ref. 1 for recent review). In mammals, there are three known members of this protein family, whereas fish and frogs express a fourth member that seems to consist of a group of closely related proteins (2-4). The characteristic tandem zinc finger domain of these proteins consists of two zinc fingers with 18 amino acids between fingers, strict intrafinger spacing of Cx8Cx5Cx3H, and a characteristic sequence motif leading into each finger of R(K)YKTEL or a closely related variant.Studies in TTP knockout mice and cells derived from them revealed that TTP acts in normal physiology to regulate the synthesis and secretion of two clinically important cytokines, tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (5-9). The increased secretion of these cytokines in the TTP knockout mice was secondary to increased steady state levels of their mRNAs, which in turn was caused by excessive stabilization of the transcripts. TTP was found to confer instability on these two transcripts by binding to the so-called class II AREs contained within the 3Ј-untranslated regions of these mRNAs (7, 10 -13). The tandem zinc finger domain was found to be the RNA binding domain, and the invariant cys...

show abstract

Section: Tristetraprolin (Ttp)mentioning

confidence: 99%

Characteristics of the Interaction of a Synthetic Human Tristetraprolin Tandem Zinc Finger Peptide with AU-rich Element-containing RNA Substrates

Blackshear

Lai²,

Kennington³

et al. 2003

Journal of Biological Chemistry

116

130

View full text Add to dashboard Cite

show abstract

“…Members of the ZFP36 gene family have been identified in several metazoans such as Drosophila , zebrafish and more recently in mollusc [19], [20], [21], [22], [23]. In the amphibian Xenopus laevis , four distinct genes that code proteins containing a tandem zinc finger domain have been identified and named xC3H-1 to 4 [24], [25].…”

Section: Introductionmentioning

confidence: 99%

Comparative Functional Analysis of ZFP36 Genes during Xenopus Development

et al. 2013

View full text Add to dashboard Cite

ZFP36 constitutes a small family of RNA binding proteins (formerly known as the TIS11 family) that target mRNA and promote their degradation. In mammals, ZFP36 proteins are encoded by four genes and, although they show similar activities in a cellular RNA destabilization assay, there is still a limited knowledge of their mRNA targets and it is not known whether or not they have redundant functions. In the present work, we have used the Xenopus embryo, a model system allowing gain- and loss-of-function studies, to investigate, whether individual ZFP36 proteins had distinct or redundant functions. We show that overexpression of individual amphibian zfp36 proteins leads to embryos having the same defects, with alteration in somites segmentation and pronephros formation. In these embryos, members of the Notch signalling pathway such as hairy2a or esr5 mRNA are down-regulated, suggesting common targets for the different proteins. We also show that mouse Zfp36 protein overexpression gives the same phenotype, indicating an evolutionary conserved property among ZFP36 vertebrate proteins. Morpholino oligonucleotide-induced loss-of-function leads to defects in pronephros formation, reduction in tubule size and duct coiling alterations for both zfp36 and zfp36l1, indicating no functional redundancy between these two genes. Given the conservation in gene structure and function between the amphibian and mammalian proteins and the conserved mechanisms for pronephros development, our study highlights a potential and hitherto unreported role of ZFP36 gene in kidney morphogenesis.

show abstract

“…The fingers are 18 amino acids apart; they have the internal spacing CX 8 CX 5 CX 3 H, where X indicates variable amino acids; and both fingers have a highly conserved lead-in sequence, R(K)YKTEL. Three such proteins have been identified to date in mammals, with a fourth member recently discovered in Xenopus and fish (2,12,13). We will refer to this small group of proteins as the CCCH tandem zinc finger (TZF) 1 domain proteins.…”

mentioning

confidence: 99%

Interactions of CCCH Zinc Finger Proteins with mRNA

Lai¹,

Kennington²,

Blackshear³

2002

Journal of Biological Chemistry

133

View full text Add to dashboard Cite

Tristetraprolin (TTP), the prototype of a small family of CCCH tandem zinc finger (TZF) domain proteins, is a physiological stimulator of instability of the mRNAs encoding tumor necrosis factor-␣ and granulocyte/macrophage colony-stimulating factor in certain cell types. TTP stimulates mRNA turnover after binding to class II AU-rich elements (AREs) within the 3-untranslated regions of both mRNAs. In turn, this binding is dependent upon the key CCCH residues in the TZF domain. To evaluate other primary sequence requirements for ARE binding in this novel mRNA-binding domain, we mutated many of the conserved residues within the TZF domain of human TTP and evaluated the effects of these mutations on RNA binding in a cell-free system and TTP-induced mRNA instability in cell transfection experiments. These mutations revealed a number of conserved amino acids that were required for binding and begin to define the primary protein sequence requirements for this novel mRNA-binding motif. Unexpectedly, all of the point mutations that prevented TTP binding to RNA also caused an increase in steady-state levels of ARE-containing mRNAs in cell transfection experiments. Actinomycin D experiments suggested that this effect was due to inhibition of mRNA turnover. Although expression of the mutant form of TTP could also inhibit the destruction of tumor necrosis factor-␣ mRNA by wild-type TTP, the primary mechanism did not involve heterodimerization with wild-type TTP because the 293 cells used in these studies express no detectable endogenous TTP. These data suggest that TTP may act, at least in part, by physically interacting with an enzyme activity or protein complex and functionally stimulating its ability to deadenylate class II ARE-containing mRNAs.The CCCH zinc finger motif has been found in proteins from organisms ranging from man to yeast (1-11). A small subset of these proteins contain two CCCH zinc fingers with the following characteristics. The fingers are 18 amino acids apart; they have the internal spacing CX 8 CX 5 CX 3 H, where X indicates variable amino acids; and both fingers have a highly conserved lead-in sequence, R(K)YKTEL. Three such proteins have been identified to date in mammals, with a fourth member recently discovered in Xenopus and fish (2, 12, 13). We will refer to this small group of proteins as the CCCH tandem zinc finger (TZF) 1 domain proteins.Our group has begun to elucidate a function for this group of proteins by analyzing the phenotype of mice deficient in tristetraprolin (TTP), the prototype of this group of proteins. These animals develop a complex phenotype consisting of cachexia, dermatitis, conjunctivitis, destructive arthritis, myeloid hyperplasia, and autoimmunity (14). Virtually all aspects of this phenotype can be prevented by the repeated injection of antibodies to tumor necrosis factor-␣ (TNF␣), implicating an effective excess of circulating TNF␣ in the pathogenesis of this condition (14). This was confirmed by studies showing that the phenotype can be largely prevented by interbreed...

show abstract

Zebrafish CTH1, a C3H zinc finger protein, is expressed in ovarian oocytes and embryos

Cited by 17 publications

References 10 publications

Characteristics of the Interaction of a Synthetic Human Tristetraprolin Tandem Zinc Finger Peptide with AU-rich Element-containing RNA Substrates

Characteristics of the Interaction of a Synthetic Human Tristetraprolin Tandem Zinc Finger Peptide with AU-rich Element-containing RNA Substrates

Comparative Functional Analysis of ZFP36 Genes during Xenopus Development

Interactions of CCCH Zinc Finger Proteins with mRNA

Contact Info

Product

Resources

About