Poly(A)-binding protein (PABP): a common viral target

Cytoplasmic PABP [poly(A)-binding protein] is a multifunctional protein with well-studied roles in mRNA translation and stability. In the present review, we examine recent evidence that the activity of PABP is altered during infection with a wide range of viruses, bringing about changes in its stability, complex formation and intracellular localization. Targeting of PABP by both RNA and DNA viruses highlights the role of PABP as a central regulator of gene expression.

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The Multifarious Role of 14-3-3 Family of Proteins in Viral Replication

Viruses ◽

10.3390/v12040436 ◽

2020 ◽

Vol 12 (4) ◽

pp. 436 ◽

Cited By ~ 4

Author(s):

Kavitha Ganesan Nathan ◽

Sunil K. Lal

Keyword(s):

Protein Interactions ◽

Viral Infections ◽

Pharmaceutical Research ◽

Host Protein ◽

Dna Viruses ◽

Wide Range ◽

Host Virus Interactions ◽

Virus Interactions ◽

Rna And Dna

The 14-3-3 proteins are a family of ubiquitous and exclusively eukaryotic proteins with an astoundingly significant number of binding partners. Their binding alters the activity, stability, localization, and phosphorylation state of a target protein. The association of 14-3-3 proteins with the regulation of a wide range of general and specific signaling pathways suggests their crucial role in health and disease. Recent studies have linked 14-3-3 to several RNA and DNA viruses that may contribute to the pathogenesis and progression of infections. Therefore, comprehensive knowledge of host–virus interactions is vital for understanding the viral life cycle and developing effective therapeutic strategies. Moreover, pharmaceutical research is already moving towards targeting host proteins in the control of virus pathogenesis. As such, targeting the right host protein to interrupt host–virus interactions could be an effective therapeutic strategy. In this review, we generated a 14-3-3 protein interactions roadmap in viruses, using the freely available Virusmentha network, an online virus–virus or virus–host interaction tool. Furthermore, we summarize the role of the 14-3-3 family in RNA and DNA viruses. The participation of 14-3-3 in viral infections underlines its significance as a key regulator for the expression of host and viral proteins.

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The Role of Translation Initiation Regulation in Haematopoiesis

Comparative and Functional Genomics ◽

10.1155/2012/576540 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Godfrey Grech ◽

Marieke von Lindern

Keyword(s):

Gene Expression ◽

Translation Initiation ◽

Translational Control ◽

Molecular Mechanisms ◽

Rna Binding ◽

Regulation Of Gene Expression ◽

Mrna Translation ◽

Translation Control ◽

Haematological Disorders

Organisation of RNAs into functional subgroups that are translated in response to extrinsic and intrinsic factors underlines a relatively unexplored gene expression modulation that drives cell fate in the same manner as regulation of the transcriptome by transcription factors. Recent studies on the molecular mechanisms of inflammatory responses and haematological disorders indicate clearly that the regulation of mRNA translation at the level of translation initiation, mRNA stability, and protein isoform synthesis is implicated in the tight regulation of gene expression. This paper outlines how these posttranscriptional control mechanisms, including control at the level of translation initiation factors and the role of RNA binding proteins, affect hematopoiesis. The clinical relevance of these mechanisms in haematological disorders indicates clearly the potential therapeutic implications and the need of molecular tools that allow measurement at the level of translational control. Although the importance of miRNAs in translation control is well recognised and studied extensively, this paper will exclude detailed account of this level of control.

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KH-type splicing regulatory protein is a new component of chromatoid body

Reproduction ◽

10.1530/rep-17-0169 ◽

2017 ◽

Vol 154 (6) ◽

pp. 723-733 ◽

Cited By ~ 1

Author(s):

Huijuan Zhang ◽

Guishuan Wang ◽

Lin Liu ◽

Xiaolin Liang ◽

Yu Lin ◽

...

Keyword(s):

Gene Expression ◽

Germ Cell ◽

Knockout Mice ◽

Binding Protein ◽

Regulatory Protein ◽

Somatic Cells ◽

Chromatoid Body ◽

Mechanistic Insight ◽

Insight Into

The chromatoid body (CB) is a specific cloud-like structure in the cytoplasm of haploid spermatids. Recent findings indicate that CB is identified as a male germ cell-specific RNA storage and processing center, but its function has remained elusive for decades. In somatic cells, KH-type splicing regulatory protein (KSRP) is involved in regulating gene expression and maturation of select microRNAs (miRNAs). However, the function of KSRP in spermatogenesis remains unclear. In this study, we showed that KSRP partly localizes in CB, as a component of CB. KSRP interacts with proteins (mouse VASA homolog (MVH), polyadenylate-binding protein 1 (PABP1) and polyadenylate-binding protein 2 (PABP2)), mRNAs (Tnp2 and Odf1) and microRNAs (microRNA-182) in mouse CB. Moreover, KSRP may regulate the integrity of CB via DDX5-miRNA-182 pathway. In addition, we found abnormal expressions of CB component in testes of Ksrp-knockout mice and of patients with hypospermatogenesis. Thus, our results provide mechanistic insight into the role of KSRP in spermatogenesis.

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A potential role for a novel ZC3H5 complex in regulating mRNA translation in Trypanosoma brucei

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014346 ◽

2020 ◽

Vol 295 (42) ◽

pp. 14291-14304

Author(s):

Kathrin Bajak ◽

Kevin Leiss ◽

Christine Clayton ◽

Esteban Erben

Keyword(s):

Gene Expression ◽

Trypanosoma Brucei ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Binding Protein ◽

Affinity Purification ◽

Critical Role ◽

Rna Binding Protein ◽

Mrna Translation

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly posttranscriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein. RNAi targeting ZC3H5 causes accumulation of precytokinetic cells followed by rapid cell death. Affinity purification and pairwise yeast two-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500, and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5′-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of “halfmer” disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of suboptimal open reading frames.

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LSD1, a double-edged sword, confers dynamic chromatin regulation but commonly promotes aberrant cell growth

F1000Research ◽

10.12688/f1000research.12169.1 ◽

2017 ◽

Vol 6 ◽

pp. 2016 ◽

Cited By ~ 13

Author(s):

Meghan M Kozub ◽

Ryan M Carr ◽

Gwen L Lomberk ◽

Martin E Fernandez-Zapico

Keyword(s):

Gene Expression ◽

Chromatin Remodeling ◽

Cellular Differentiation ◽

Critical Role ◽

Histone Demethylase ◽

Epigenetic Changes ◽

Lysine Specific Demethylase ◽

Wide Range ◽

Histone Modifying Enzymes

Histone-modifying enzymes play a critical role in chromatin remodeling and are essential for influencing several genome processes such as gene expression and DNA repair, replication, and recombination. The discovery of lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, dramatically revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in a wide range of biological operations, including development, cellular differentiation, embryonic pluripotency, and disease (for example, cancer). This mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its involvement in epigenetic changes throughout development, and its importance in physiological and pathological processes.

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Roles of Elongator Dependent tRNA Modification Pathways in Neurodegeneration and Cancer

Genes ◽

10.3390/genes10010019 ◽

2018 ◽

Vol 10 (1) ◽

pp. 19 ◽

Cited By ~ 18

Author(s):

Harmen Hawer ◽

Alexander Hammermeister ◽

Keerthiraju Ravichandran ◽

Sebastian Glatt ◽

Raffael Schaffrath ◽

...

Keyword(s):

Gene Expression ◽

Human Disease ◽

Messenger Rna ◽

Environmental Changes ◽

Mrna Translation ◽

Regulatory Control ◽

Trna Modification ◽

Positive Role ◽

Trna Modifications

Transfer RNA (tRNA) is subject to a multitude of posttranscriptional modifications which can profoundly impact its functionality as the essential adaptor molecule in messenger RNA (mRNA) translation. Therefore, dynamic regulation of tRNA modification in response to environmental changes can tune the efficiency of gene expression in concert with the emerging epitranscriptomic mRNA regulators. Several of the tRNA modifications are required to prevent human diseases and are particularly important for proper development and generation of neurons. In addition to the positive role of different tRNA modifications in prevention of neurodegeneration, certain cancer types upregulate tRNA modification genes to sustain cancer cell gene expression and metastasis. Multiple associations of defects in genes encoding subunits of the tRNA modifier complex Elongator with human disease highlight the importance of proper anticodon wobble uridine modifications (xm5U34) for health. Elongator functionality requires communication with accessory proteins and dynamic phosphorylation, providing regulatory control of its function. Here, we summarized recent insights into molecular functions of the complex and the role of Elongator dependent tRNA modification in human disease.

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An Essential Role of cAMP Response Element Binding Protein in Ginsenoside Rg1-Mediated Inhibition of Na+/Glucose Cotransporter 1 Gene Expression

Molecular Pharmacology ◽

10.1124/mol.114.097352 ◽

2015 ◽

Vol 88 (6) ◽

pp. 1072-1083 ◽

Cited By ~ 14

Author(s):

Chun-Wen Wang ◽

Shih-Chieh Su ◽

Shu-Fen Huang ◽

Yu-Chuan Huang ◽

Fang-Na Chan ◽

...

Keyword(s):

Gene Expression ◽

Essential Role ◽

Binding Protein ◽

Camp Response Element Binding ◽

Ginsenoside Rg1 ◽

Camp Response Element ◽

Response Element ◽

Element Binding Protein

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5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1708044114 ◽

2017 ◽

Vol 114 (37) ◽

pp. E7812-E7821 ◽

Cited By ~ 50

Author(s):

Marian Mellén ◽

Pinar Ayata ◽

Nathaniel Heintz

Keyword(s):

Gene Expression ◽

Binding Protein ◽

Binding Specificity ◽

Chromatin Organization ◽

Postmitotic Neurons ◽

Cg Dinucleotides

5-hydroxymethylcytosine (5hmC) occurs at maximal levels in postmitotic neurons, where its accumulation is cell-specific and correlated with gene expression. Here we demonstrate that the distribution of 5hmC in CG and non-CG dinucleotides is distinct and that it reflects the binding specificity and genome occupancy of methylcytosine binding protein 2 (MeCP2). In expressed gene bodies, accumulation of 5hmCG acts in opposition to 5mCG, resulting in “functional” demethylation and diminished MeCP2 binding, thus facilitating transcription. Non-CG hydroxymethylation occurs predominantly in CA dinucleotides (5hmCA) and it accumulates in regions flanking active enhancers. In these domains, oxidation of 5mCA to 5hmCA does not alter MeCP2 binding or expression of adjacent genes. We conclude that the role of 5-hydroxymethylcytosine in postmitotic neurons is to functionally demethylate expressed gene bodies while retaining the role of MeCP2 in chromatin organization.

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Overlapping and Unique Roles for C-Terminal Binding Protein 1 (CtBP1) and CtBP2 during Mouse Development

Molecular and Cellular Biology ◽

10.1128/mcb.22.15.5296-5307.2002 ◽

2002 ◽

Vol 22 (15) ◽

pp. 5296-5307 ◽

Cited By ~ 199

Author(s):

Jeffrey D. Hildebrand ◽

Philippe Soriano

Keyword(s):

Gene Expression ◽

Transcription Factors ◽

Genetic Interaction ◽

Binding Protein ◽

Biological Processes ◽

Vertebrate Development ◽

Mouse Development ◽

Axial Patterning ◽

Wide Range

ABSTRACT The C-terminal binding protein (CtBP) family of proteins has been linked to multiple biological processes through their association with numerous transcription factors. We generated mice harboring mutations in both Ctbp1 and Ctbp2 to address the in vivo function of CtBPs during vertebrate development. Ctbp1 mutant mice are small but viable and fertile, whereas Ctbp2-null mice show defects in axial patterning and die by E10.5 due to aberrant extraembryonic development. Mice harboring various combinations of Ctbp1 and Ctbp2 mutant alleles exhibit dosage-sensitive defects in a wide range of developmental processes. The strong genetic interaction, as well as transcription assays with CtBP-deficient cells, indicates that CtBPs have overlapping roles in regulating gene expression. We suggest that the observed phenotypes reflect the large number of transcription factors whose activities are compromised in the absence of CtBP.

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