scholarly journals A computational study of RNA binding and specificity in the tandem zinc finger domain of TIS11d

2010 ◽  
Vol 19 (6) ◽  
pp. 1222-1234 ◽  
Author(s):  
Brittany R. Morgan ◽  
Francesca Massi
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Computational Study ◽  
Zinc Finger Domain ◽  
Tandem Zinc Finger

scholarly journals Structural Basis of the Disorder in the Tandem Zinc Finger Domain of the RNA-Binding Protein Tristetraprolin

2016 ◽  
Vol 12 (10) ◽  
pp. 4717-4725 ◽  
Author(s):  
Davide Tavella ◽  
Laura M. Deveau ◽  
Troy W. Whitfield ◽  
Francesca Massi
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Structural Basis ◽  
Zinc Finger Domain ◽  
Tandem Zinc Finger

scholarly journals The tandem zinc finger RNA binding domain of members of the tristetraprolin protein family

2019 ◽  
Vol 10 (4) ◽  
pp. e1531 ◽  
Author(s):  
Wi S. Lai ◽  
Melissa L. Wells ◽  
Lalith Perera ◽  
Perry J. Blackshear
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Protein Family ◽  
Binding Domain ◽  
Rna Binding Domain ◽  
Tandem Zinc Finger

scholarly journals APLF (C2orf13) Is a Novel Component of Poly(ADP-Ribose) Signaling in Mammalian Cells

2008 ◽  
Vol 28 (14) ◽  
pp. 4620-4628 ◽  
Author(s):  
Stuart L. Rulten ◽  
Felipe Cortes-Ledesma ◽  
Liandi Guo ◽  
Natasha J. Iles ◽  
Keith W. Caldecott
Keyword(s):  
Zinc Finger ◽  
Mammalian Cells ◽  
Strand Break ◽  
Zinc Finger Domain ◽  
Chromosomal Damage ◽  
Chromosomal Dna ◽  
Fha Domain ◽  
Break Repair ◽  
Dna Strand ◽  
Tandem Zinc Finger

ABSTRACT APLF is a novel protein of unknown function that accumulates at sites of chromosomal DNA strand breakage via forkhead-associated (FHA) domain-mediated interactions with XRCC1 and XRCC4. APLF can also accumulate at sites of chromosomal DNA strand breaks independently of the FHA domain via an unidentified mechanism that requires a highly conserved C-terminal tandem zinc finger domain. Here, we show that the zinc finger domain binds tightly to poly(ADP-ribose), a polymeric posttranslational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Protein poly(ADP-ribosyl)ation is tightly regulated and defects in either its synthesis or degradation slow global rates of chromosomal single-strand break repair. Interestingly, APLF negatively affects poly(ADP-ribosyl)ation in vitro, and this activity is dependent on its capacity to bind the polymer. In addition, transient overexpression in human A549 cells of full-length APLF or a C-terminal fragment encoding the tandem zinc finger domain greatly suppresses the appearance of poly(ADP-ribose), in a zinc finger-dependent manner. We conclude that APLF can accumulate at sites of chromosomal damage via zinc finger-mediated binding to poly(ADP-ribose) and is a novel component of poly(ADP-ribose) signaling in mammalian cells.

scholarly journals Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Cedric Leyrat ◽  
Max Renner ◽  
Karl Harlos ◽  
Juha T Huiskonen ◽  
Jonathan M Grimes
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Dynamic Equilibrium ◽  
Conformational Dynamics ◽  
Adenosine Monophosphate ◽  
Zinc Finger Domain ◽  
Rna Sequences ◽  
Solution Structures ◽  
Closed Conformation ◽  
Dynamics Simulations

The M2-1 protein of human metapneumovirus (HMPV) is a zinc-binding transcription antiterminator which is highly conserved among pneumoviruses. We report the structure of tetrameric HMPV M2-1. Each protomer features a N-terminal zinc finger domain and an α-helical tetramerization motif forming a rigid unit, followed by a flexible linker and an α-helical core domain. The tetramer is asymmetric, three of the protomers exhibiting a closed conformation, and one an open conformation. Molecular dynamics simulations and SAXS demonstrate a dynamic equilibrium between open and closed conformations in solution. Structures of adenosine monophosphate- and DNA- bound M2-1 establish the role of the zinc finger domain in base-specific recognition of RNA. Binding to ‘gene end’ RNA sequences stabilized the closed conformation of M2-1 leading to a drastic shift in the conformational landscape of M2-1. We propose a model for recognition of gene end signals and discuss the implications of these findings for transcriptional regulation in pneumoviruses.

scholarly journals A mRNA localized to the vegetal cortex of Xenopus oocytes encodes a protein with a nanos-like zinc finger domain

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 377-386 ◽  
Author(s):  
L. Mosquera ◽  
C. Forristall ◽  
Y. Zhou ◽  
M.L. King
Keyword(s):  
Cell Fate ◽  
Zinc Finger ◽  
Regional Differences ◽  
Xenopus Oocytes ◽  
Rna Binding ◽  
Protein Product ◽  
Posterior Pole ◽  
Cortical Region ◽  
Zinc Finger Domain ◽  
Vegetal Cortex

mRNAs concentrated in specific regions of the oocyte have been found to encode determinants that specify cell fate. We show that an intermediate filament fraction isolated from Xenopus stage VI oocytes specifically contains, in addition to Vg1 RNA, a new localized mRNA, Xcat-2. Like Vg1, Xcat-2 is found in the vegetal cortical region, is inherited by the vegetal blasomeres during development, and is degraded very early in development. Sequence analysis suggests that Xcat-2 encodes a protein that belongs to the CCHC RNA-binding family of zinc finger proteins. Interestingly, the closest known relative to Xcat-2 in this family is nanos, an RNA localized to the posterior pole of the Drosophila oocyte whose protein product suppresses the translation of the transcription factor hunchback. The localized and maternally restricted expression of Xcat-2 RNA suggests a role for its protein in setting up regional differences in gene expression that occur early in development.

Targeted Disruption of Zfp36l2, Encoding a CCCH Tandem Zinc Finger RNA-Binding Protein, Results in Defective Hematopoiesis.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1401-1401
Author(s):  
Deborah J. Stumpo ◽  
Hal E. Broxmeyer ◽  
Scott Cooper ◽  
Giao Hangoc ◽  
Peter D. Aplan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Zinc Finger ◽  
Rna Binding ◽  
Fetal Liver ◽  
Liver Cells ◽  
Hematopoietic Progenitors ◽  
Hematopoietic System ◽  
Fetal Liver Cells ◽  
Tandem Zinc Finger

Abstract Members of the tristetraprolin (TTP) family of tandem CCCH finger proteins can bind to AU-rich elements in the 3′-untranslated region of mRNAs, leading to their deadenylation and subsequent degradation. In previous work, we disrupted the first exon of one of the four mouse TTP family members, Zfp36l2 (Tis11d, Brf2, Erf2), resulting in the production of decreased levels of a truncated protein lacking the first 29 amino acids. These mice exhibited complete female infertility, with embryos not progressing past the two-cell stage. In order to establish a true null phenotype for this gene, we have generated mice completely lacking the second exon, encoding the RNA-binding tandem zinc finger domain, resulting in a true knockout (KO) with complete lack of mRNA and protein. Surprisingly, these mice exhibited a completely unexpected phenotype involving the development of the hematopoietic system; they appeared otherwise anatomically normal. Homozygous Zfp36l2 KO mice on a mixed C57Bl/6 – 129SvEv background were born with normal Mendelian frequency but generally died about two weeks after birth, apparently from intestinal or other hemorrhage. Analysis of peripheral blood from KO mice at two weeks of age showed significant decreases in red cells (2.3 fold), white cells (2.1 fold), and platelets (11 fold). Flow cytometric analysis of spleen cells demonstrated significant decreases in myeloid cells (Gr-1+; Gr-1+/Mac-1+; 4 fold) and megakaryocytes (CD41+; 14 fold), as well as in c-Kit+ hematopoietic progenitors, without changes in lymphoid cell populations. Bone sections from rare surviving adult mice exhibited hematopoietic cell depletion. In addition, analysis of bone marrow revealed nine-fold decreases in lin-/Sca-1+/c-Kit+ cells; colony forming assays revealed that no hematopoietic progenitors grew from the KO bone marrow, compared to an average of 54 colonies per mouse from the wild-type (WT) mice. We therefore analyzed the development of the hematopoietic system. To do this, we cultured fetal liver cells in semisolid media that supported the proliferation and differentiation of multipotential and lineage-committed hematopoietic progenitors. There were significant decreases in the numbers of erythroid (BFU-E, 10-fold), granulocyte- macrophage (CFU-GM, 32-fold), granulocyte macrophage/macrophage (CFU-GM/M, 14-fold), and multipotential (CFU-GEMM, 14-fold) progenitor cells obtained from Zfp36l2 KO fetal liver cells at embryonic day (E) 14.5 as compared to WT cells from littermates. There were also statistically significant decreases in these progenitors in heterozygous mice compared to WT, suggesting a gene dosage effect. Similar studies of yolk sacs from E11.5 mice revealed significant decreases in myeloid (CFU-GM, 2-fold) and multipotential (CFU-GEMM, 1.7-fold) progenitors in the KO yolk sacs. Primitive hematopoiesis was unaffected, as assessed by in vitro colony forming assays with E8-8.25 yolk sac cells. Competitive reconstitution experiments demonstrated that Zfp36l2 KO fetal cells from E14.5 mice were markedly defective in reconstituting the hematopoietic system of lethally irradiated recipients after 1, 2 and 6 months of follow-up; engraftment rates for these dates were, respectively, 45% (WT) vs. 8% (KO); 65% vs. 3%; and 86% vs. 1%. These studies demonstrated that the development of the definitive hematopoietic system was severely adversely affected in the Zfp36l2 KO mice. This led to the hypothesis that elimination of the RNA destabilizing protein ZFP36L2 leads to the accumulation of one or more transcripts that are toxic to hematopoiesis. To explore this hypothesis, microarray analyses were performed on RNA samples from fetal liver at E14.5. We identified 239 significantly elevated transcripts in the KO samples, including several possible candidates for direct binding targets for ZFP36L2. In addition, 175 transcripts were significantly down-regulated in the KO fetal livers, in many cases in pathways of hematopoiesis or platelet development and function. These results are currently being validated by a variety of functional biochemical approaches, and are being supplemented by analogous microarray assays using transcripts from E11.5 yolk sacs. These data establish Zfp36l2 as a critical modulator of definitive hematopoiesis, and suggest a novel regulatory pathway involving control of mRNA stability in the life cycle of hematopoietic stem and progenitor cells.

scholarly journals Recognition of Polyadenosine RNA by the Zinc Finger Domain of Nuclear Poly(A) RNA-binding Protein 2 (Nab2) Is Required for Correct mRNA 3′-End Formation*

2010 ◽  
Vol 285 (34) ◽  
pp. 26022-26032 ◽  
Author(s):  
Seth M. Kelly ◽  
Sara W. Leung ◽  
Luciano H. Apponi ◽  
Anna M. Bramley ◽  
Elizabeth J. Tran ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Zinc Finger Domain

scholarly journals Mutational and Structural Analysis of the Tandem Zinc Finger Domain of Tristetraprolin

2013 ◽  
Vol 289 (1) ◽  
pp. 565-580 ◽  
Author(s):  
Wi S. Lai ◽  
Lalith Perera ◽  
Stephanie N. Hicks ◽  
Perry J. Blackshear
Keyword(s):  
Structural Analysis ◽  
Zinc Finger ◽  
Zinc Finger Domain ◽  
Tandem Zinc Finger

scholarly journals A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Thomas Pohlmann ◽  
Sebastian Baumann ◽  
Carl Haag ◽  
Mario Albrecht ◽  
Michael Feldbrügge
Keyword(s):  
Zinc Finger ◽  
Membrane Trafficking ◽  
Molecular Motors ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Detailed Knowledge ◽  
Zinc Finger Domain ◽  
Domain Protein ◽  
Dependent Transport

An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.

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