scholarly journals A Trypanosoma cruzi Zinc Finger protein that controls expression of epimastigote specific genes and affects metacyclogenesis

2020 ◽  
Author(s):  
Thais Silva Tavares ◽  
Fernanda Lins Brandão Mügge ◽  
Viviane Grazielle-Silva ◽  
Bruna Mattioly Valente ◽  
Wanessa Moreira Goes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Trypanosoma Cruzi ◽  
Zinc Finger ◽  
Rna Binding ◽  
Environmental Changes ◽  
Zinc Finger Protein ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Control Of Gene Expression ◽  
Genes Encoding

SummaryTrypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and control of gene expression relies on mechanisms acting at the post-transcriptional level. Transcriptome analyses comparing epimastigote, trypomastigote and intracellular amastigote stages revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBP), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP (TcZH3H12) that contains a zinc finger domain, and whose transcripts are upregulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Comparative transcriptome analysis revealed a TcZC3H12-dependent expression of epimastigote specific genes encoding amino acid transporters and proteins associated with differentiation (PAD), among others. RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.

scholarly journals A Trypanosoma cruzi zinc finger protein that is implicated in the control of epimastigote-specific gene expression and metacyclogenesis

Parasitology ◽  
2020 ◽  
pp. 1-15
Author(s):  
Thais S. Tavares ◽  
Fernanda L. B. Mügge ◽  
Viviane Grazielle-Silva ◽  
Bruna M. Valente ◽  
Wanessa M. Goes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Zinc Finger ◽  
Rna Binding ◽  
Environmental Changes ◽  
Negative Regulator ◽  
Specific Gene ◽  
Genes Encoding ◽  
Transcriptome Analyses

Abstract Trypanosoma cruzi has three biochemically and morphologically distinct developmental stages that are programmed to rapidly respond to environmental changes the parasite faces during its life cycle. Unlike other eukaryotes, Trypanosomatid genomes contain protein coding genes that are transcribed into polycistronic pre-mRNAs and have their expression controlled by post-transcriptional mechanisms. Transcriptome analyses comparing three stages of the T. cruzi life cycle revealed changes in gene expression that reflect the parasite adaptation to distinct environments. Several genes encoding RNA binding proteins (RBPs), known to act as key post-transcriptional regulatory factors, were also differentially expressed. We characterized one T. cruzi RBP, named TcZH3H12, which contains a zinc finger domain and is up-regulated in epimastigotes compared to trypomastigotes and amastigotes. TcZC3H12 knockout (KO) epimastigotes showed decreased growth rates and increased capacity to differentiate into metacyclic trypomastigotes. Transcriptome analyses comparing wild type and TcZC3H12 KOs revealed a TcZC3H12-dependent expression of epimastigote-specific genes such as genes encoding amino acid transporters and proteins associated with differentiation (PADs). RNA immunoprecipitation assays showed that transcripts from the PAD family interact with TcZC3H12. Taken together, these findings suggest that TcZC3H12 positively regulates the expression of genes involved in epimastigote proliferation and also acts as a negative regulator of metacyclogenesis.

scholarly journals RsmV a small non-coding regulatory RNA in Pseudomonas aeruginosa that sequesters RsmA and RsmF from target mRNAs

2018 ◽  
Author(s):  
Kayley H. Janssen ◽  
Manisha R. Diaz ◽  
Cindy J. Gode ◽  
Matthew C. Wolfgang ◽  
Timothy L. Yahr
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Binding Sites ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Secretion System ◽  
Transcriptional Level ◽  
Type Vi Secretion System ◽  
Control Of Gene Expression ◽  
Target Mrnas

ABSTRACTThe Gram-negative opportunistic pathogen Pseudomonas aeruginosa has distinct genetic programs that favor either acute or chronic virulence gene expression. Acute virulence is associated with twitching and swimming motility, expression of a type III secretion system (T3SS), and the absence of alginate, Psl, or Pel polysaccharide production. Traits associated with chronic infection include growth as a biofilm, reduced motility, and expression of a type VI secretion system (T6SS). The Rsm post-transcriptional regulatory system plays an important role in the inverse control of phenotypes associated with acute and chronic virulence. RsmA and RsmF are RNA-binding proteins that interact with target mRNAs to control gene expression at the post-transcriptional level. Previous work found that RsmA activity is controlled by at least three small, non-coding regulatory RNAs (RsmW, RsmY, and RsmZ). In this study, we took an in-silico approach to identify additional sRNAs that might function in the sequestration of RsmA and/or RsmF and identified RsmV, a 192 nt transcript with four predicted RsmA/RsmF consensus binding sites. RsmV is capable of sequestering RsmA and RsmF in vivo to activate translation of tssA1, a component of the T6SS, and to inhibit T3SS gene expression. Each of the predicted RsmA/RsmF consensus binding sites contribute to RsmV activity. Electrophoretic mobility shifts assays show that RsmF binds RsmV with >10-fold higher affinity than RsmY and RsmZ. Gene expression studies revealed that the temporal expression pattern of RsmV differs from RsmW, RsmY, and RsmZ. These findings suggest that each sRNA may play distinct roles in controlling RsmA and RsmF activity.IMPORTANCEThe role of RsmF in post-transcriptional control of gene expression remains enigmatic. While numerous rsmA-dependent phenotypes are more pronounced in an rsmAF double mutant, deletion of rsmF alone has only modest effects. Understanding mechanisms that control RsmF activity will provide insight into additional roles for RsmF. In the current study we identify RsmV as an sRNA that controls RsmA and RsmF activity, and show that RsmV, RsmW, RsmY, and RsmZ are differentially expressed during growth.

scholarly journals The Tristetraprolin Family of RNA-Binding Proteins in Cancer: Progress and Future Prospects

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1539 ◽  
Author(s):  
Yogesh Saini ◽  
Jian Chen ◽  
Sonika Patial
Keyword(s):  
Gene Expression ◽  
Transcriptional Regulation ◽  
Zinc Finger ◽  
Binding Proteins ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Finger Protein ◽  
Post Transcriptional Regulation

Post-transcriptional regulation of gene expression plays a key role in cellular proliferation, differentiation, migration, and apoptosis. Increasing evidence suggests dysregulated post-transcriptional gene expression as an important mechanism in the pathogenesis of cancer. The tristetraprolin family of RNA-binding proteins (RBPs), which include Zinc Finger Protein 36 (ZFP36; commonly referred to as tristetraprolin (TTP)), Zinc Finger Protein 36 like 1 (ZFP36L1), and Zinc Finger Protein 36 like 2 (ZFP36L2), play key roles in the post-transcriptional regulation of gene expression. Mechanistically, these proteins function by binding to the AU-rich elements within the 3′-untranslated regions of their target mRNAs and, in turn, increasing mRNA turnover. The TTP family RBPs are emerging as key regulators of multiple biological processes relevant to cancer and are aberrantly expressed in numerous human cancers. The TTP family RBPs have tumor-suppressive properties and are also associated with cancer prognosis, metastasis, and resistance to chemotherapy. Herein, we summarize the various hallmark molecular traits of cancers that are reported to be regulated by the TTP family RBPs. We emphasize the role of the TTP family RBPs in the regulation of trait-associated mRNA targets in relevant cancer types/cell lines. Finally, we highlight the potential of the TTP family RBPs as prognostic indicators and discuss the possibility of targeting these TTP family RBPs for therapeutic benefits.

scholarly journals Regulatory interplay between RNase III and asRNAs in E. coli; the case of AsflhD and the master regulator of motility, flhDC

2021 ◽  
Author(s):  
Maxence Lejars ◽  
Joel CAILLET ◽  
Maude Guillier ◽  
Jacqueline A Plumbridge ◽  
Eliane HAJNSDORF
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Rnase Iii ◽  
Master Regulator ◽  
E Coli ◽  
Genes Encoding ◽  
Rna Chaperones

In order to respond to ever-changing environmental cues, bacteria have evolved resilient regulatory mechanisms controlling gene expression. At the post-transcriptional level, this is achieved by a combination of RNA-binding proteins, such as ribonucleases (RNases) and RNA chaperones, and regulatory RNAs including antisense RNAs (asRNAs). AsRNAs bound to their complementary mRNA are primary targets for the double-strand-specific endoribonuclease, RNase III. By comparing primary and processed transcripts in an rnc strain, mutated for RNase III, and its isogenic wild type strain, we detected several asRNAs. We confirmed the existence of RNase III-sensitive asRNA for crp, ompR, phoP and flhD genes, encoding master regulators of gene expression. AsflhD, the asRNA to the master regulator of motility flhDC, is slightly induced under heat-shock conditions in a sigma24 (RpoE)-dependent manner. We demonstrate that expression of AsflhD asRNA is involved in the transcriptional attenuation of flhD and thus participates in the control of the whole motility cascade. This study demonstrates that AsflhD and RNase III are additional players in the complex regulation ensuring a tight control of flagella synthesis and motility.

scholarly journals trans Repression of the Human Metallothionein IIA Gene Promoter by PZ120, a Novel 120-Kilodalton Zinc Finger Protein

1999 ◽  
Vol 19 (1) ◽  
pp. 680-689 ◽  
Author(s):  
Chih-Min Tang ◽  
Jennifer Westling ◽  
Edward Seto
Keyword(s):  
Zinc Finger ◽  
Dna Sequences ◽  
Transcription Initiation ◽  
Zinc Finger Protein ◽  
Gene Promoter ◽  
Initiation Site ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Finger Protein ◽  
Eukaryotic Organisms

ABSTRACT Metallothioneins are small, highly conserved, cysteine-rich proteins that bind a variety of metal ions. They are found in virtually all eukaryotic organisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as binding sites fortrans-acting factors such as Sp1, AP1, AP2, AP4, and the glucocorticoid receptor, the hMTIIA promoter contains eight consensus metal response element sequences. We report here the cloning of a novel zinc finger protein with a molecular mass of 120 kDa (PZ120) that interacts specifically with the hMTIIA transcription initiation site. The PZ120 protein is ubiquitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcription factors. Intriguingly, we found that a region of PZ120 outside of the zinc finger domain can bind specifically to the hMTIIA DNA. Using transient-transfection analysis, we found that PZ120 repressed transcription of the hMTIIA promoter. These results suggest that the hMTIIA gene is regulated by an additional negative regulator that has not been previously described.

scholarly journals FOG-2, a Heart- and Brain-Enriched Cofactor for GATA Transcription Factors

1999 ◽  
Vol 19 (6) ◽  
pp. 4495-4502 ◽  
Author(s):  
Jian-rong Lu ◽  
Timothy A. McKinsey ◽  
Hongtao Xu ◽  
Da-zhi Wang ◽  
James A. Richardson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Hematopoietic Cell ◽  
Related Factor ◽  
Control Of Gene Expression ◽  
Cell Lineages ◽  
Gata Transcription Factors

ABSTRACT Members of the GATA family of zinc finger transcription factors have been shown to play important roles in the control of gene expression in a variety of cell types. GATA-1, -2, and -3 are expressed primarily in hematopoietic cell lineages and are required for proliferation and differentiation of multiple hematopoietic cell types, whereas GATA-4, -5, and -6 are expressed in the heart, where they activate cardiac muscle structural genes. Friend of GATA-1 (FOG) is a multitype zinc finger protein that interacts with GATA-1 and serves as a cofactor for GATA-1-mediated transcription. FOG is coexpressed with GATA-1 in developing erythroid and megakaryocyte cell lineages and cooperates with GATA-1 to control erythropoiesis. We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis. FOG-2 interacts with GATA factors, and interaction of GATA-4 and FOG-2 results in either synergistic activation or repression of GATA-dependent cardiac promoters, depending on the specific promoter and the cell type in which they are tested. The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors.

scholarly journals Characterization of the RNA-Binding Protein TcSgn1 in Trypanosoma cruzi

2021 ◽  
Vol 9 (5) ◽  
pp. 986
Author(s):  
Camila Oliveira ◽  
André P. Gerber ◽  
Samuel Goldenberg ◽  
Lysangela R. Alves
Keyword(s):  
Gene Expression ◽  
Trypanosoma Cruzi ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Regulation Of Gene Expression ◽  
Rna Binding Protein ◽  
Transcriptional Level ◽  
Rna Recognition Motif ◽  
Ribonucleoprotein Complexes

RNA-binding proteins (RBPs) participate in several steps of post-transcriptional regulation of gene expression, such as splicing, messenger RNA transport, mRNA localization, and translation. Gene-expression regulation in trypanosomatids occurs primarily at the post-transcriptional level, and RBPs play important roles in the process. Here, we characterized the RBP TcSgn1, which contains one RNA recognition motif (RRM). TcSgn1 is a close ortholog of yeast Saccharomyces cerevisiae protein ScSgn1, which plays a role in translational regulation in the cytoplasm. We found that TcSgn1 in Trypanosoma cruzi is localized in the nucleus in exponentially growing epimastigotes. By performing immunoprecipitation assays of TcSgn1, we identified hundreds of mRNAs associated with the protein, a significant fraction of them coding for nucleic acids binding, transcription, and endocytosis proteins. In addition, we show that TcSgn1 is capable of interacting directly with the poly(A) tail of the mRNAs. The study of parasites under nutritional stress showed that TcSgn1 was localized in cytoplasmic granules in addition to localizing in the nucleus. Similar to ScSgn1, we observed that TcSgn1 also interacts with the PABP1 protein, suggesting that this protein may play a role in regulating gene expression in T. cruzi. Taken together, our results show that RNA-binding protein TcSgn1 is part of ribonucleoprotein complexes associated with nuclear functions, stress response, and RNA metabolism.

scholarly journals Ectopic targeting of CG DNA methylation in Arabidopsis with the bacterial SssI methyltransferase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wanlu Liu ◽  
Javier Gallego-Bartolomé ◽  
Yuxing Zhou ◽  
Zhenhui Zhong ◽  
Ming Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Basic Research ◽  
Crop Plant ◽  
Open Chromatin ◽  
Histone Marks ◽  
It Impacts ◽  
Finger Protein

AbstractThe ability to target epigenetic marks like DNA methylation to specific loci is important in both basic research and in crop plant engineering. However, heritability of targeted DNA methylation, how it impacts gene expression, and which epigenetic features are required for proper establishment are mostly unknown. Here, we show that targeting the CG-specific methyltransferase M.SssI with an artificial zinc finger protein can establish heritable CG methylation and silencing of a targeted locus in Arabidopsis. In addition, we observe highly heritable widespread ectopic CG methylation mainly over euchromatic regions. This hypermethylation shows little effect on transcription while it triggers a mild but significant reduction in the accumulation of H2A.Z and H3K27me3. Moreover, ectopic methylation occurs preferentially at less open chromatin that lacks positive histone marks. These results outline general principles of the heritability and interaction of CG methylation with other epigenomic features that should help guide future efforts to engineer epigenomes.

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