scholarly journals Small Trypanosome RNA-Binding Proteins TbUBP1 and TbUBP2 Influence Expression of F-Box Protein mRNAs in Bloodstream Trypanosomes

2007 ◽  
Vol 6 (11) ◽  
pp. 1964-1978 ◽  
Author(s):  
Claudia Hartmann ◽  
Corinna Benz ◽  
Stefanie Brems ◽  
Louise Ellis ◽  
Van-Duc Luu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Degradation ◽  
Rna Recognition Motif ◽  
Mrna Levels ◽  
Control Of Gene Expression ◽  
F Box Protein ◽  
Cyclin F

ABSTRACT In the African trypanosome Trypanosoma brucei nearly all control of gene expression is posttranscriptional; sequences in the 3′-untranslated regions of mRNAs determine the steady-state mRNA levels by regulation of RNA turnover. Here we investigate the roles of two related proteins, TbUBP1 and TbUBP2, containing a single RNA recognition motif, in trypanosome gene expression. TbUBP1 and TbUBP2 are in the cytoplasm and nucleus, comprise ca. 0.1% of the total protein, and are not associated with polysomes or RNA degradation enzymes. Overexpression of TbUBP2 upregulated the levels of several mRNAs potentially involved in cell division, including the CFB1 mRNA, which encodes a protein with a cyclin F-box domain. CFB1 regulation was mediated by the 3′-untranslated region and involved stabilization of the mRNA. Depletion of TbUBP2 and TbUBP1 inhibited growth and downregulated expression of the cyclin F box protein gene CFB2; trans splicing was unaffected. The results of pull-down assays indicated that all tested mRNAs were bound to TbUBP2 or TbUBP1, with some preference for CFB1. We suggest that TbUBP1 and TbUBP2 may be relatively nonspecific RNA-binding proteins and that specific effects of overexpression or depletion could depend on competition between various different proteins for RNA binding.

238 RNA BINDING PROTEIN EXPRESSION IN CULTURED EARLY BOVINE EMBRYOS

2010 ◽  
Vol 22 (1) ◽  
pp. 277
Author(s):  
L. A. Favetta ◽  
E. Van de Laar ◽  
W. A. King ◽  
J. LaMarre
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Bovine Embryo ◽  
Rt Pcr ◽  
Control Of Gene Expression ◽  
Morula Stage ◽  
Bovine Oocytes

The control of gene expression in the early embryo requires a highly regulated turnover of specific mRNA, particularly those of maternal origin, as the embryo becomes transcriptionally autonomous. In cattle, the period during which maternal transcripts persist can last 72 to 96 h or longer, suggesting a dynamic, regulated interplay between factors that protect transcripts before this point and those that subsequently facilitate decay. Some decay pathways for specific embryonic transcripts are now known, but many are not. In somatic cells, mRNA decay is often mediated by interactions between defined sequence elements (ARE) in the 3′ untranslated region of important target genes and specific RNA-binding proteins (AUBP) that promote or inhibit decay of the associated transcript. These have not been extensively characterized in embryos. We hypothesized that changes in the pattern of expression of one or several AUBP in the developing bovine embryo would support a role for these proteins in mRNA turnover and the control of gene expression. We, therefore, evaluated the expression of different AUBP (HuR, AUF1, TTP) in bovine oocytes and early embryos in vitro. Bovine oocytes obtained at slaughter were matured, fertilized, and cultured using standard protocols. Oocytes and embryos from different stages were either placed in Trizol for subsequent RNA isolation and RT-PCR analysis or fixed in 4% paraformaldehyde and subsequently processed for immunohistochemical detection of AUBP. Analysis by RT-PCR revealed that AUF1, an mRNA destabilizing protein, was expressed at all stages examined (immature oocyte, mature oocyte, 2 to 4 cells, 8 to 16 cells, morulae, and blastocyst) except in morulae. Another mRNA destabilizing protein, TTP, was expressed at the morula stage only. An mRNA stabilizing factor, HuR, was expressed at all stages except the morula. Immunohistochemical analysis revealed that the pattern of protein expression for AUF1 and TTP essentially mirrored that observed at the RNA level as detected by RT-PCR. Together, these results show that AUBP expression in the early bovine embryo is dynamic, with RNA-binding proteins present at all times during development and changes in expression evident at the morula stage. This suggests that modification of presynthesized (i.e. maternal) AUBP is likely to control mRNA decay during the maternal to embryonic transition (8-cell stage) and that the expression of TTP at the morula stage might mark the onset of embryonic control of mRNA stability. Research was supported by NSERC, OMAFRA, and the Canada Research Chairs Program.

scholarly journals Cip1 and Cip2 Are Novel RNA-Recognition-Motif Proteins That Counteract Csx1 Function during Oxidative Stress

2006 ◽  
Vol 17 (3) ◽  
pp. 1176-1183 ◽  
Author(s):  
Victoria Martín ◽  
Miguel A. Rodríguez-Gabriel ◽  
W. Hayes McDonald ◽  
Stephen Watt ◽  
John R. Yates ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Stress Response ◽  
Protein Identification ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Bzip Transcription Factor ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Control Of Gene Expression

Eukaryotic cells reprogram their global patterns of gene expression in response to stress. Recent studies in Schizosaccharomyces pombe showed that the RNA-binding protein Csx1 plays a central role in controlling gene expression during oxidative stress. It does so by stabilizing atf1+ mRNA, which encodes a subunit of a bZIP transcription factor required for gene expression during oxidative stress. Here, we describe two related proteins, Cip1 and Cip2, that were identified by multidimensional protein identification technology (MudPIT) as proteins that coprecipitate with Csx1. Cip1 and Cip2 are cytoplasmic proteins that have RNA recognition motifs (RRMs). Neither protein is essential for viability, but a cip1Δ cip2Δ strain grows poorly and has altered cellular morphology. Genetic epistasis studies and whole genome expression profiling show that Cip1 and Cip2 exert posttranscriptional control of gene expression in a manner that is counteracted by Csx1. Notably, the sensitivity of csx1Δ cells to oxidative stress and their inability to induce expression of Atf1-dependent genes are partially rescued by cip1Δ and cip2Δ mutations. This study emphasizes the importance of a modulated mRNA stability in the eukaryotic stress response pathways and adds new information to the role of RNA-binding proteins in the oxidative stress response.

scholarly journals EBV noncoding RNA EBER2 interacts with host RNA-binding proteins to regulate viral gene expression

2016 ◽  
Vol 113 (12) ◽  
pp. 3221-3226 ◽  
Author(s):  
Nara Lee ◽  
Therese A. Yario ◽  
Jessica S. Gao ◽  
Joan A. Steitz
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Lytic Replication ◽  
Nuclear Bodies ◽  
Viral Gene ◽  
Mrna Levels ◽  
Binding Studies

Epstein–Barr virus (EBV) produces a highly abundant noncoding RNA called EBV-encoded RNA 2 (EBER2) that interacts indirectly with the host transcription factor paired box protein 5 (PAX5) to regulate viral latent membrane protein 1/2 (LMP1/2) gene expression as well as EBV lytic replication. To identify intermediary proteins, we isolated EBER2–PAX5-containing complexes and analyzed the protein components by mass spectrometry. The top candidates include three host proteins splicing factor proline and glutamine rich (SFPQ), non-POU domain-containing octamer-binding protein (NONO), and RNA binding motif protein 14 (RBM14), all reported to be components of nuclear bodies called paraspeckles. In vivo RNA–protein crosslinking indicates that SFPQ and RBM14 contact EBER2 directly. Binding studies using recombinant proteins demonstrate that SFPQ and NONO associate with PAX5, potentially bridging its interaction with EBER2. Similar to EBER2 or PAX5 depletion, knockdown of any of the three host RNA-binding proteins results in the up-regulation of viral LMP2A mRNA levels, supporting a physiologically relevant interaction of these newly identified factors with EBER2 and PAX5. Identification of these EBER2-interacting proteins enables the search for cellular noncoding RNAs that regulate host gene expression in a manner similar to EBER2.

scholarly journals Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sarah Gilbertson ◽  
Joel D Federspiel ◽  
Ella Hartenian ◽  
Ileana M Cristea ◽  
Britt Glaunsinger
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Mrna Decay ◽  
Binding Proteins ◽  
Rna Binding ◽  
Nuclear Translocation ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Protein Localization ◽  
Rna Degradation

Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.

scholarly journals The Major RNA-Binding Protein ProQ Impacts Virulence Gene Expression inSalmonella entericaSerovar Typhimurium

mBio ◽  
2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander J. Westermann ◽  
Elisa Venturini ◽  
Mikael E. Sellin ◽  
Konrad U. Förstner ◽  
Wolf-Dietrich Hardt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Enteric Bacteria ◽  
Host Cells ◽  
Dependent Manner ◽  
Control Of Gene Expression

ABSTRACTFinO domain proteins such as ProQ of the model pathogenSalmonella entericahave emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes asSalmonellainfects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone inSalmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ forSalmonellapathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs.IMPORTANCEThe protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. Asin vitrowork continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapesSalmonellavirulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria.

Regulation of B-cell differentiation by microRNAs and RNA-binding proteins

2008 ◽  
Vol 36 (6) ◽  
pp. 1191-1193 ◽  
Author(s):  
Alexander Ademokun ◽  
Martin Turner
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
B Cell Differentiation ◽  
Control Of Gene Expression ◽  
Gm Csf ◽  
Factor Α

Post-transcriptional control of gene expression is an important mechanism for maintaining cellular homoeostasis and regulating the immune response to infection. It allows control of mRNA abundance, translation and localization. Mechanisms for post-transcriptional control involve RNA-binding proteins and miRNAs (microRNAs). The TTP(tristetraprolin) family of proteins recognize and bind AU-rich elements. Deletion of TTP led to a systemic autoimmune syndrome with excess circulating TNFα (tumour necrosis factor α) and GM-CSF (granulocyte/macrophage colony-stimulating factor) due to aberrantly stabilized mRNA. The family may also have a role in control of lymphocyte development and function. miRNAs regulate gene expression by promoting decay or inhibiting translation of transcripts with base pair complementarity. The importance of miRNAs in lymphocytes is highlighted by the T-cell-specific deletion of Dicer, an enzyme required for miRNA-mediated processing and from the phenotype of bic (B-cell integration cluster)/miR-155 (miRNA 155)-deficient mice.

Control of mRNA degradation in trypanosomes

2008 ◽  
Vol 36 (3) ◽  
pp. 520-521 ◽  
Author(s):  
Christine Clayton ◽  
Angela Schwede ◽  
Mhairi Stewart ◽  
Ana Robles ◽  
Corinna Benz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Interference ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Mrna Degradation ◽  
Rna Recognition ◽  
Rna Recognition Motifs ◽  
Control Of Gene Expression ◽  
Recognition Motifs

Control of gene expression in trypanosomes relies almost exclusively on post-transcriptional mechanisms. Trypanosomes have the normal enzymes for mRNA decay: both the exosome and a 5′–3′-exoribonuclease are important in the degradation of very unstable transcripts, whereas the CAF1/NOT complex plays a major role in the degradation of all mRNAs tested. Targeted RNA interference screening was used to identify RNA-binding proteins that regulate mRNA degradation, and it revealed roles for proteins with RNA recognition motifs or pumilio domains.

Posttranscription Initiation Control of Gene Expression Mediated by Bacterial RNA-Binding Proteins

2019 ◽  
Vol 73 (1) ◽  
pp. 43-67 ◽  
Author(s):  
Paul Babitzke ◽  
Ying-Jung Lai ◽  
Andrew J. Renda ◽  
Tony Romeo
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Tertiary Structure ◽  
Rna Binding Proteins ◽  
True Nature ◽  
Control Of Gene Expression ◽  
Global Regulators ◽  
Rna Targets ◽  
Bacterial Rna

RNA-binding proteins play vital roles in regulating gene expression and cellular physiology in all organisms. Bacterial RNA-binding proteins can regulate transcription termination via attenuation or antitermination mechanisms, while others can repress or activate translation initiation by affecting ribosome binding. The RNA targets for these proteins include short repeated sequences, longer single-stranded sequences, RNA secondary or tertiary structure, and a combination of these features. The activity of these proteins can be influenced by binding of metabolites, small RNAs, or other proteins, as well as by phosphorylation events. Some of these proteins regulate specific genes, while others function as global regulators. As the regulatory mechanisms, components, targets, and signaling circuitry surrounding RNA-binding proteins have become better understood, in part through rapid advances provided by systems approaches, a sense of the true nature of biological complexity is becoming apparent, which we attempt to capture for the reader of this review.

scholarly journals Auto-regulatory feedback by RNA-binding proteins

2019 ◽  
Vol 11 (10) ◽  
pp. 930-939 ◽  
Author(s):  
Michaela Müller-McNicoll ◽  
Oliver Rossbach ◽  
Jingyi Hui ◽  
Jan Medenbach
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Feedback Regulation ◽  
Control Of Gene Expression ◽  
Cell Fate Decisions

Abstract RNA-binding proteins (RBPs) are key regulators in post-transcriptional control of gene expression. Mutations that alter their activity or abundance have been implicated in numerous diseases such as neurodegenerative disorders and various types of cancer. This highlights the importance of RBP proteostasis and the necessity to tightly control the expression levels and activities of RBPs. In many cases, RBPs engage in an auto-regulatory feedback by directly binding to and influencing the fate of their own mRNAs, exerting control over their own expression. For this feedback control, RBPs employ a variety of mechanisms operating at all levels of post-transcriptional regulation of gene expression. Here we review RBP-mediated autogenous feedback regulation that either serves to maintain protein abundance within a physiological range (by negative feedback) or generates binary, genetic on/off switches important for e.g. cell fate decisions (by positive feedback).

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