scholarly journals Crosstalk between RNA-Binding Proteins and Immune Microenvironment Revealed Two RBP Regulatory Patterns with Distinct Immunophenotypes in Periodontitis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Lu Xing ◽  
Guanqun Meng ◽  
Tian Chen ◽  
Xiaoqi Zhang ◽  
Ding Bai ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Spearman Correlation ◽  
Protein Protein Interactions ◽  
Immune Microenvironment ◽  
Potential Impact ◽  
Highly Correlated ◽  
Signaling Activation

Periodontitis is an inflammatory disease whose pathogenesis is closely related with immunology. RNA-binding proteins (RBPs) were found to play crucial roles in immunity. Therefore, we aimed to investigate the potential impact of RBPs in the immune microenvironment in periodontitis. The differential expressions of RBPs in periodontitis and healthy samples were determined and were used to construct an RBP-based classifier for periodontitis using logistic regression. The correlations between RBPs and immune characteristics were investigated by the Spearman correlation. Unsupervised clustering was conducted to identify the RBP regulatory patterns. RBP-related genes were identified by WGCNA, while biological distinctions were revealed by GSVA and GO. 24 dysregulated RBPs were identified, from which a 12-RBP classifier was established to distinguish periodontitis with AUC of 0.942. Close protein-protein interactions and expression correlations were observed especially between SPATS2 and ISG20. ISG20 and ESRP1 were found to be highly correlated with immunocyte infiltration, immune signaling activation, and HLA expressions in periodontitis. Two distinct RBP regulatory patterns were identified with different immune and other biological characteristics in periodontitis. Our findings indicate a significant impact of RBPs in shaping the immune microenvironment in periodontitis, which might bring new insights into the understanding of immune mechanisms in the pathogenesis of periodontitis.

scholarly journals rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins

2020 ◽  
Author(s):  
Benjamin Lang ◽  
Jae-Seong Yang ◽  
Mireia Garriga-Canut ◽  
Silvia Speroni ◽  
Maria Gili ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Interaction Networks ◽  
Sequence Motifs ◽  
Protein Protein Interactions ◽  
Binding Interaction ◽  
Transcriptional Gene Regulation

AbstractRNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactions in vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacently in vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks.Graphical abstract

scholarly journals Interactions between the double-stranded RNA-binding proteins TRBP and PACT define the Medipal domain that mediates protein-protein interactions

RNA Biology ◽  
2008 ◽  
Vol 5 (2) ◽  
pp. 92-103 ◽  
Author(s):  
Ghislaine Laraki ◽  
Guerline Clerzius ◽  
Aïcha Daher ◽  
Carlos Melendez-Peña ◽  
Sylvanne Daniels ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Protein Interactions ◽  
Double Stranded Rna

scholarly journals The increasing diversity of functions attributed to the SAFB family of RNA-/DNA-binding proteins

2016 ◽  
Vol 473 (23) ◽  
pp. 4271-4288 ◽  
Author(s):  
Michael Norman ◽  
Caroline Rivers ◽  
Youn-Bok Lee ◽  
Jalilah Idris ◽  
James Uney
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cellular Stress Response ◽  
Regulatory Rna ◽  
Protein Protein Interactions ◽  
Attachment Region ◽  
Dna Elements ◽  
Scaffold Attachment Region

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein–protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins.

PlncRNADB: A Repository of Plant lncRNAs and lncRNA-RBP Protein Interactions

2019 ◽  
Vol 14 (7) ◽  
pp. 621-627 ◽  
Author(s):  
Youhuang Bai ◽  
Xiaozhuan Dai ◽  
Tiantian Ye ◽  
Peijing Zhang ◽  
Xu Yan ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Populus Trichocarpa ◽  
Noncoding Rnas ◽  
Reference Database ◽  
Protein Coding ◽  
Arabidopsis Lyrata ◽  
User Friendly

Background: Long noncoding RNAs (lncRNAs) are endogenous noncoding RNAs, arbitrarily longer than 200 nucleotides, that play critical roles in diverse biological processes. LncRNAs exist in different genomes ranging from animals to plants. Objective: PlncRNADB is a searchable database of lncRNA sequences and annotation in plants. Methods: We built a pipeline for lncRNA prediction in plants, providing a convenient utility for users to quickly distinguish potential noncoding RNAs from protein-coding transcripts. Results: More than five thousand lncRNAs are collected from four plant species (Arabidopsis thaliana, Arabidopsis lyrata, Populus trichocarpa and Zea mays) in PlncRNADB. Moreover, our database provides the relationship between lncRNAs and various RNA-binding proteins (RBPs), which can be displayed through a user-friendly web interface. Conclusion: PlncRNADB can serve as a reference database to investigate the lncRNAs and their interaction with RNA-binding proteins in plants. The PlncRNADB is freely available at http://bis.zju.edu.cn/PlncRNADB/.

scholarly journals RNA regulons and the RNA-protein interaction network

2012 ◽  
Vol 3 (5) ◽  
pp. 403-414 ◽  
Author(s):  
Jochen Imig ◽  
Alexander Kanitz ◽  
André P. Gerber
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Protein Interaction Network ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Interaction Network ◽  
Coordinated Control ◽  
Non Coding Rnas ◽  
Rna Interaction

AbstractThe development of genome-wide analysis tools has prompted global investigation of the gene expression program, revealing highly coordinated control mechanisms that ensure proper spatiotemporal activity of a cell’s macromolecular components. With respect to the regulation of RNA transcripts, the concept of RNA regulons, which – by analogy with DNA regulons in bacteria – refers to the coordinated control of functionally related RNA molecules, has emerged as a unifying theory that describes the logic of regulatory RNA-protein interactions in eukaryotes. Hundreds of RNA-binding proteins and small non-coding RNAs, such as microRNAs, bind to distinct elements in target RNAs, thereby exerting specific and concerted control over posttranscriptional events. In this review, we discuss recent reports committed to systematically explore the RNA-protein interaction network and outline some of the principles and recurring features of RNA regulons: the coordination of functionally related mRNAs through RNA-binding proteins or non-coding RNAs, the modular structure of its components, and the dynamic rewiring of RNA-protein interactions upon exposure to internal or external stimuli. We also summarize evidence for robust combinatorial control of mRNAs, which could determine the ultimate fate of each mRNA molecule in a cell. Finally, the compilation and integration of global protein-RNA interaction data has yielded first insights into network structures and provided the hypothesis that RNA regulons may, in part, constitute noise ‘buffers’ to handle stochasticity in cellular transcription.

scholarly journals Targeting RNA Binding Proteins Involved in Neurodegeneration

2013 ◽  
Vol 18 (9) ◽  
pp. 967-983 ◽  
Author(s):  
Maurizio Romano ◽  
Emanuele Buratti
Keyword(s):  
Protein Interactions ◽  
Rna Processing ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Correct Identification ◽  
Protein Protein Interactions ◽  
Aggregation Processes ◽  
Cellular Pathways ◽  
Screening Approaches

Dysfunctions at the level of RNA processing have recently been shown to play a fundamental role in the pathogenesis of many neurodegenerative diseases. Several proteins responsible for these dysfunctions (TDP-43, FUS/TLS, and hnRNP A/Bs) belong to the nuclear class of heterogeneous ribonucleoproteins (hnRNPs) that predominantly function as general regulators of both coding and noncoding RNA metabolism. The discovery of the importance of these factors in mediating neuronal death has represented a major paradigmatic shift in our understanding of neurodegenerative processes. As a result, these discoveries have also opened the way toward novel biomolecular screening approaches in our search for therapeutic options. One of the major hurdles in this search is represented by the correct identification of the most promising targets to be prioritized. These may include aberrant aggregation processes, protein-protein interactions, RNA-protein interactions, or specific cellular pathways altered by disease. In this review, we discuss these four major options together with their various advantages and drawbacks.

scholarly journals iSUMO - integrative prediction of functionally relevant SUMOylation events

2016 ◽  
Author(s):  
Xiaotong Yao ◽  
Shuvadeep Maity ◽  
Shashank Gandhi ◽  
Marcin Imielenski ◽  
Christine Vogel
Keyword(s):  
Protein Interactions ◽  
Large Scale ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
False Positive Rate ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Positive Rate ◽  
Protein Nucleic Acid ◽  
Scale Experiment

AbstractPost-translational modifications by the Small Ubiquitin-like Modifier (SUMO) are essential for diverse cellular functions. Large-scale experiment and sequence-based predictions have identified thousands of SUMOylated proteins. However, the overlap between the datasets is small, suggesting many false positives with low functional relevance. Therefore, we integrated ~800 sequence features and protein characteristics such as cellular function and protein-protein interactions in a machine learning approach to score likely functional SUMOylation events (iSUMO). iSUMO is trained on a total of 24 large-scale datasets, and it predicts 2,291 and 706 SUMO targets in human and yeast, respectively. These estimates are five times higher than what existing sequence-based tools predict at the same 5% false positive rate. Protein-protein and protein-nucleic acid interactions are highly predictive of protein SUMOylation, supporting a role of the modification in protein complex formation. We note the marked prevalence of SUMOylation amongst RNA-binding proteins. We validate iSUMO predictions by experimental or other evidence. iSUMO therefore represents a comprehensive tool to identify high-confidence, functional SUMOylation events for human and yeast.

scholarly journals Systematic discovery and functional interrogation of SARS-CoV-2 viral RNA-host protein interactions during infection

2020 ◽  
Author(s):  
Ryan A. Flynn ◽  
Julia A. Belk ◽  
Yanyan Qi ◽  
Yuki Yasumoto ◽  
Cameron O. Schmitz ◽  
...  
Keyword(s):  
Protein Interaction ◽  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Viral Rna ◽  
Host Protein ◽  
List Type ◽  
Genome Wide ◽  
A Genome

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a pandemic with growing global mortality. There is an urgent need to understand the molecular pathways required for host infection and anti-viral immunity. Using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS), we identified 309 host proteins that bind the SARS-CoV-2 RNA during active infection. Integration of this data with viral ChIRP-MS data from three other positive-sense RNA viruses defined pan-viral and SARS-CoV-2-specific host interactions. Functional interrogation of these factors with a genome-wide CRISPR screen revealed that the vast majority of viral RNA-binding proteins protect the host from virus-induced cell death, and we identified known and novel anti-viral proteins that regulate SARS-CoV-2 pathogenicity. Finally, our RNA-centric approach demonstrated a physical connection between SARS-CoV-2 RNA and host mitochondria, which we validated with functional and electron microscopy data, providing new insights into a more general virus-specific protein logic for mitochondrial interactions. Altogether, these data provide a comprehensive catalogue of SARS-CoV-2 RNA-host protein interactions, which may inform future studies to understand the mechanisms of viral pathogenesis, as well as nominate host pathways that could be targeted for therapeutic benefit.Highlights· ChIRP-MS of SARS-CoV-2 RNA identifies a comprehensive viral RNA-host protein interaction network during infection across two species· Comparison to RNA-protein interaction networks with Zika virus, dengue virus, and rhinovirus identify SARS-CoV-2-specific and pan-viral RNA protein complexes and highlights distinct intracellular trafficking pathways· Intersection of ChIRP-MS and genome-wide CRISPR screens identify novel SARS-CoV-2-binding proteins with pro- and anti-viral function· Viral RNA-RNA and RNA-protein interactions reveal specific SARS-CoV-2-mediated mitochondrial dysfunction during infection

scholarly journals Capturing RNA–protein interaction via CRUIS

2020 ◽  
Vol 48 (9) ◽  
pp. e52-e52 ◽  
Author(s):  
Ziheng Zhang ◽  
Weiping Sun ◽  
Tiezhu Shi ◽  
Pengfei Lu ◽  
Min Zhuang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Dna Damage ◽  
Protein Interactions ◽  
Noncoding Rna ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Living Cells ◽  
Innovative Methods ◽  
Rna Biology

Abstract No RNA is completely naked from birth to death. RNAs function with and are regulated by a range of proteins that bind to them. Therefore, the development of innovative methods for studying RNA–protein interactions is very important. Here, we developed a new tool, the CRISPR-based RNA-United Interacting System (CRUIS), which captures RNA–protein interactions in living cells by combining the power of CRISPR and PUP-IT, a novel proximity targeting system. In CRUIS, dCas13a is used as a tracker to target specific RNAs, while proximity enzyme PafA is fused to dCas13a to label the surrounding RNA-binding proteins, which are then identified by mass spectrometry. To identify the efficiency of CRUIS, we employed NORAD (Noncoding RNA activated by DNA damage) as a target, and the results show that a similar interactome profile of NORAD can be obtained as by using CLIP (crosslinking and immunoprecipitation)-based methods. Importantly, several novel NORAD RNA-binding proteins were also identified by CRUIS. The use of CRUIS facilitates the study of RNA–protein interactions in their natural environment, and provides new insights into RNA biology.

scholarly journals Nuclear RNP complex assembly initiates cytoplasmic RNA localization

2004 ◽  
Vol 165 (2) ◽  
pp. 203-211 ◽  
Author(s):  
Tracy L. Kress ◽  
Young J. Yoon ◽  
Kimberly L. Mowry
Keyword(s):  
Protein Interactions ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Localization ◽  
Rna Sequences ◽  
Cytoplasmic Rna ◽  
Rnp Complex ◽  
Maternal Mrnas ◽  
Protein Components

Cytoplasmic localization of mRNAs is a widespread mechanism for generating cell polarity and can provide the basis for patterning during embryonic development. A prominent example of this is localization of maternal mRNAs in Xenopus oocytes, a process requiring recognition of essential RNA sequences by protein components of the localization machinery. However, it is not yet clear how and when such protein factors associate with localized RNAs to carry out RNA transport. To trace the RNA–protein interactions that mediate RNA localization, we analyzed RNP complexes from the nucleus and cytoplasm. We find that an early step in the localization pathway is recognition of localized RNAs by specific RNA-binding proteins in the nucleus. After transport into the cytoplasm, the RNP complex is remodeled and additional transport factors are recruited. These results suggest that cytoplasmic RNA localization initiates in the nucleus and that binding of specific RNA-binding proteins in the nucleus may act to target RNAs to their appropriate destinations in the cytoplasm.

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