scholarly journals TREND-DB—a transcriptome-wide atlas of the dynamic landscape of alternative polyadenylation

2020 ◽  
Vol 49 (D1) ◽  
pp. D243-D253
Author(s):  
Federico Marini ◽  
Denise Scherzinger ◽  
Sven Danckwardt
Keyword(s):  
Gene Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Therapeutic Potential ◽  
Alternative Polyadenylation ◽  
Functional Enrichment ◽  
Rna Modifications ◽  
Individual Transcript ◽  
Dynamic Landscape ◽  
Transcriptional Gene Regulation

Abstract Alternative polyadenylation (APA) profoundly expands the transcriptome complexity. Perturbations of APA can disrupt biological processes, ultimately resulting in devastating disorders. A major challenge in identifying mechanisms and consequences of APA (and its perturbations) lies in the complexity of RNA 3′ end processing, involving poorly conserved RNA motifs and multi-component complexes consisting of far more than 50 proteins. This is further complicated in that RNA 3′ end maturation is closely linked to transcription, RNA processing and even epigenetic (histone/DNA/RNA) modifications. Here, we present TREND-DB (http://shiny.imbei.uni-mainz.de:3838/trend-db), a resource cataloging the dynamic landscape of APA after depletion of >170 proteins involved in various facets of transcriptional, co- and post-transcriptional gene regulation, epigenetic modifications and further processes. TREND-DB visualizes the dynamics of transcriptome 3′ end diversification (TREND) in a highly interactive manner; it provides a global APA network map and allows interrogating genes affected by specific APA-regulators and vice versa. It also permits condition-specific functional enrichment analyses of APA-affected genes, which suggest wide biological and clinical relevance across all RNAi conditions. The implementation of the UCSC Genome Browser provides additional customizable layers of gene regulation accounting for individual transcript isoforms (e.g. epigenetics, miRNA-binding sites and RNA-binding proteins). TREND-DB thereby fosters disentangling the role of APA for various biological programs, including potential disease mechanisms, and helps identify their diagnostic and therapeutic potential.

scholarly journals TREND-DB – A Transcriptome-wide Atlas of the Dynamic Landscape of Alternative Polyadenylation

2020 ◽  
Author(s):  
Federico Marini ◽  
Denise Scherzinger ◽  
Sven Danckwardt
Keyword(s):  
Gene Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Therapeutic Potential ◽  
Alternative Polyadenylation ◽  
Functional Enrichment ◽  
Rna Modifications ◽  
Posttranscriptional Gene Regulation ◽  
Individual Transcript ◽  
Dynamic Landscape

AbstractAlternative polyadenylation (APA) profoundly expands the transcriptome complexity. Perturbations of APA can disrupt biological processes, ultimately resulting in devastating disorders. A major challenge in identifying mechanisms and consequences of APA (and its perturbations) lies in the complexity of RNA 3’end processing, involving poorly conserved RNA motifs and multi-component complexes consisting of far more than 50 proteins. This is further complicated in that RNA 3’end maturation is closely linked to transcription, RNA processing, and even epigenetic (histone/DNA/RNA) modifications. Here we present TREND-DB (http://shiny.imbei.uni-mainz.de:3838/trend-db), a resource cataloging the dynamic landscape of APA after depletion of >170 proteins involved in various facets of transcriptional, co- and posttranscriptional gene regulation, epigenetic modifications, and further processes. TREND-DB visualizes the dynamics of transcriptome 3’end diversification (TREND) in a highly interactive manner; it provides a global APA network map and allows interrogating genes affected by specific APA-regulators, and vice versa. It also permits condition-specific functional enrichment analyses of APA-affected genes, which suggest wide biological and clinical relevance across all RNAi conditions. The implementation of the UCSC Genome Browser provides additional customizable layers of gene regulation accounting for individual transcript isoforms (e.g. epigenetics, miRNA binding sites, RNA-binding proteins). TREND-DB thereby fosters disentangling the role of APA for various biological programs, including potential disease mechanisms, and helps to identify their diagnostic and therapeutic potential.

scholarly journals Alternative polyadenylation: methods, mechanism, function, and role in cancer

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Yi Zhang ◽  
Lian Liu ◽  
Qiongzi Qiu ◽  
Qing Zhou ◽  
Jinwang Ding ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Single Gene ◽  
Alternative Polyadenylation ◽  
Length Change ◽  
Suppressor Gene ◽  
Gene Expressions ◽  
Related Factors ◽  
Mrna Maturation

AbstractOccurring in over 60% of human genes, alternative polyadenylation (APA) results in numerous transcripts with differing 3’ends, thus greatly expanding the diversity of mRNAs and of proteins derived from a single gene. As a key molecular mechanism, APA is involved in various gene regulation steps including mRNA maturation, mRNA stability, cellular RNA decay, and protein diversification. APA is frequently dysregulated in cancers leading to changes in oncogenes and tumor suppressor gene expressions. Recent studies have revealed various APA regulatory mechanisms that promote the development and progression of a number of human diseases, including cancer. Here, we provide an overview of four types of APA and their impacts on gene regulation. We focus particularly on the interaction of APA with microRNAs, RNA binding proteins and other related factors, the core pre-mRNA 3’end processing complex, and 3’UTR length change. We also describe next-generation sequencing methods and computational tools for use in poly(A) signal detection and APA repositories and databases. Finally, we summarize the current understanding of APA in cancer and provide our vision for future APA related research.

Plant PUF RNA-binding proteins: A wealth of diversity for post-transcriptional gene regulation

Plant Science ◽  
2020 ◽  
Vol 297 ◽  
pp. 110505
Author(s):  
Chris R. Joshna ◽  
Pritha Saha ◽  
Dilini Atugala ◽  
Gordon Chua ◽  
Douglas G. Muench
Keyword(s):  
Gene Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Transcriptional Gene Regulation

scholarly journals Role of PUM RNA-Binding Proteins in Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 129
Author(s):  
Maciej J. Smialek ◽  
Erkut Ilaslan ◽  
Marcin P. Sajek ◽  
Jadwiga Jaruzelska
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Alternative Polyadenylation ◽  
Cancer Therapies ◽  
Target Mrnas ◽  
Non Coding Rna ◽  
Specific Localization ◽  
Transcriptional Gene Regulation ◽  
Cancer Tissues

Until recently, post-transcriptional gene regulation (PTGR), in contrast to transcriptional regulation, was not extensively explored in cancer, even though it seems to be highly important. PUM proteins are well described in the PTGR of several organisms and contain the PUF RNA-binding domain that recognizes the UGUANAUA motif, located mostly in the 3′ untranslated region (3′UTR) of target mRNAs. Depending on the protein cofactors recruited by PUM proteins, target mRNAs are directed towards translation, repression, activation, degradation, or specific localization. Abnormal profiles of PUM expression have been shown in several types of cancer, in some of them being different for PUM1 and PUM2. This review summarizes the dysregulation of PUM1 and PUM2 expression in several cancer tissues. It also describes the regulatory mechanisms behind the activity of PUMs, including cooperation with microRNA and non-coding RNA machineries, as well as the alternative polyadenylation pathway. It also emphasizes the importance of future studies to gain a more complete picture of the role of PUM proteins in different types of cancer. Such studies may result in identification of novel targets for future cancer therapies.

scholarly journals RNA-binding proteins and post-transcriptional gene regulation

FEBS Letters ◽  
2008 ◽  
Vol 582 (14) ◽  
pp. 1977-1986 ◽  
Author(s):  
Tina Glisovic ◽  
Jennifer L. Bachorik ◽  
Jeongsik Yong ◽  
Gideon Dreyfuss
Keyword(s):  
Gene Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Transcriptional Gene Regulation

scholarly journals S1-Domain RNA-Binding Protein (CvfD) Is a New Post-Transcriptional Regulator That Mediates Cold Sensitivity, Phosphate Transport, and Virulence in Streptococcus pneumoniae D39

2020 ◽  
Author(s):  
Dhriti Sinha ◽  
Jiaqi J. Zheng ◽  
Ho-Ching Tiffany Tsui ◽  
John D. Richardson ◽  
Nicholas R. De Lay ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Binding Protein ◽  
Phosphate Transport ◽  
Cold Sensitivity ◽  
Rna Biology ◽  
Transcriptional Gene Regulation ◽  
Pleiotropic Regulator

ABSTRACTPost-transcriptional gene regulation often involves RNA-binding proteins that modulate mRNA translation and/or stability either directly through protein-RNA interactions or indirectly by facilitating the annealing of small regulatory RNAs (sRNAs). The human pathogen Streptococcus pneumoniae D39 (pneumococcus) does not encode homologs to RNA-binding proteins known to be involved in promoting sRNA stability and function, such as Hfq or ProQ, even though it contains genes for at least 112 sRNAs. However, the pneumococcal genome contains genes for other RNA-binding proteins, including at least six S1-domain proteins; ribosomal protein S1 (rpsA), polynucleotide phosphorylase (pnpA), RNase R (rnr), and three proteins of unknown functions. Here, we characterize the function of one of these conserved, yet uncharacterized S1-domain proteins, SPD_1366, which we have renamed CvfD (Conserved virulence factor D), since loss of this protein results in an attenuation of virulence in a murine pneumonia model. We report that deletion of cvfD impacts expression of 144 transcripts including the pst1 operon, encoding the phosphate transport system 1 in S. pneumoniae. We further show that CvfD post-transcriptionally regulates the PhoU2 master regulator of the pneumococcal dual phosphate transport system by binding phoU2 mRNA and impacting PhoU2 translation. CvfD not only controls expression of phosphate transporter genes, but also functions as a pleiotropic regulator that impacts cold sensitivity and the expression of sRNAs and genes involved in diverse cellular functions, including manganese uptake and zinc efflux. Together, our data show that CvfD exerts a broad impact on pneumococcal physiology and virulence, partly by post-transcriptional gene regulation.SIGNIFICANCERecent advances have led to the identification of numerous sRNAs in the major human respiratory pathogen, S. pneumoniae. However, little is known about the functions of most sRNAs or RNA-binding proteins involved in RNA biology in pneumococcus. In this paper, we characterize the phenotypes and one target of the S1-domain RNA-binding protein CvfD, a homolog of “general-stress protein 13” identified, but not extensively characterized in other Firmicute species. Pneumococcal CvfD is a broadly pleiotropic regulator, whose absence results in misregulation of divalent cation homeostasis, reduced translation of the PhoU2 master regulator of phosphate uptake, altered metabolism and sRNA amounts, cold sensitivity, and attenuation of virulence. These findings underscore the critical roles of RNA biology in pneumococcal physiology and virulence.

scholarly journals Defining the RBPome of T helper cells to study higher order post-transcriptional gene regulation

2020 ◽  
Author(s):  
Kai P. Hoefig ◽  
Alexander Reim ◽  
Christian Gallus ◽  
Elaine H. Wong ◽  
Gesine Behrens ◽  
...  
Keyword(s):  
T Cells ◽  
Gene Regulation ◽  
T Cell ◽  
T Helper Cells ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Higher Order ◽  
T Helper ◽  
Transcriptional Gene Regulation ◽  
Human And Mouse

AbstractPost-transcriptional gene regulation is complex, dynamic and ensures proper T cell function. The targeted transcripts can simultaneously respond to various factors as evident for Icos, an mRNA regulated by several RNA binding proteins (RBPs), including Roquin. However, fundamental information about the entire RBPome involved in post-transcriptional gene regulation in T cells is lacking. Here, we applied global RNA interactome capture (RNA-IC) and orthogonal organic phase separation (OOPS) to human and mouse primary T cells and identified the core T cell RBPome. This defined 798 mouse and 801 human proteins as RBPs, unexpectedly containing signaling proteins like Stat1, Stat4 and Vav1. Based on the vicinity to Roquin-1 in proximity labeling experiments, we selected ∼50 RBPs for testing coregulation of Roquin targets. Induced expression of these candidate RBPs in wildtype and Roquin-deficient T cells unraveled several Roquin-independent contributions, but also revealed Celf1 as a new Roquin-1-dependent and target-specific coregulator of Icos.One sentence statementWe provide an atlas of RNA-binding proteins in human and mouse T helper cells as a resource for studying higher order post-transcriptional gene regulation.

scholarly journals Proteome-wide Profiling of RNA-Binding Protein Responses to flg22 Reveals Novel Components of Plant Immunity

2020 ◽  
Author(s):  
Marcel Bach-Pages ◽  
Honglin Chen ◽  
Nattapong Sanguankiattichai ◽  
Riccardo Soldan ◽  
Farnusch Kaschani ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Pseudomonas Syringae ◽  
Plant Resistance ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Plant Immunity ◽  
Rna Binding Protein ◽  
Post Translational Modifications ◽  
Transcriptional Gene Regulation ◽  
Mutant Lines

RNA-binding proteins (RBPs) play critical roles in post-transcriptional gene regulation and are known to contribute to plant immunity. To understand the responses of cellular RBPs to an immune elicitor, we applied RNA interactome capture to Arabidopsis leaves treated with flg22. Strikingly, flg22 induced a pervasive remodelling of the cellular RBPome affecting 186 proteins. Flg22-responsive RBPs included classical RBPs involved in RNA metabolism as well as non-canonical RBPs. RBP responders detected after 2h of treatment are enriched in putative sites for post-translational modifications, which may play a regulatory role. By contrast, changes in RBP abundance becomes increasingly important for the RBPome responses to flg22 after 12h. Plant resistance to Pseudomonas syringae is strongly altered in mutant lines lacking individual flg22-responsive RBPs, supporting the importance of RBP dynamics in plant immunity. This study provides a comprehensive and systematic census of flg22 responsive plant RBPs, discovering novel components of plant immunity.

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