scholarly journals A Census and Categorization Method of Epitranscriptomic Marks

2020 ◽  
Vol 21 (13) ◽  
pp. 4684
Author(s):  
Julia Mathlin ◽  
Loredana Le Pera ◽  
Teresa Colombo
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Messenger Rnas ◽  
Rna Modifications ◽  
Chemical Modifications ◽  
Rna Molecules ◽  
Transcriptional Regulatory ◽  
Functional Relevance

In the past few years, thorough investigation of chemical modifications operated in the cells on ribonucleic acid (RNA) molecules is gaining momentum. This new field of research has been dubbed “epitranscriptomics”, in analogy to best-known epigenomics, to stress the potential of ensembles of RNA modifications to constitute a post-transcriptional regulatory layer of gene expression orchestrated by writer, reader, and eraser RNA-binding proteins (RBPs). In fact, epitranscriptomics aims at identifying and characterizing all functionally relevant changes involving both non-substitutional chemical modifications and editing events made to the transcriptome. Indeed, several types of RNA modifications that impact gene expression have been reported so far in different species of cellular RNAs, including ribosomal RNAs, transfer RNAs, small nuclear RNAs, messenger RNAs, and long non-coding RNAs. Supporting functional relevance of this largely unknown regulatory mechanism, several human diseases have been associated directly to RNA modifications or to RBPs that may play as effectors of epitranscriptomic marks. However, an exhaustive epitranscriptome’s characterization, aimed to systematically classify all RNA modifications and clarify rules, actors, and outcomes of this promising regulatory code, is currently not available, mainly hampered by lack of suitable detecting technologies. This is an unfortunate limitation that, thanks to an unprecedented pace of technological advancements especially in the sequencing technology field, is likely to be overcome soon. Here, we review the current knowledge on epitranscriptomic marks and propose a categorization method based on the reference ribonucleotide and its rounds of modifications (“stages”) until reaching the given modified form. We believe that this classification scheme can be useful to coherently organize the expanding number of discovered RNA modifications.

scholarly journals RNA-Binding Proteins in Pulmonary Hypertension

2020 ◽  
Vol 21 (11) ◽  
pp. 3757 ◽  
Author(s):  
Hui Zhang ◽  
R. Dale Brown ◽  
Kurt R. Stenmark ◽  
Cheng-Jun Hu
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Critical Role ◽  
Apoptosis Resistance ◽  
Aberrant Expression ◽  
Expression Of Genes

Pulmonary hypertension (PH) is a life-threatening disease characterized by significant vascular remodeling and aberrant expression of genes involved in inflammation, apoptosis resistance, proliferation, and metabolism. Effective therapeutic strategies are limited, as mechanisms underlying PH pathophysiology, especially abnormal expression of genes, remain unclear. Most PH studies on gene expression have focused on gene transcription. However, post-transcriptional alterations have been shown to play a critical role in inflammation and metabolic changes in diseases such as cancer and systemic cardiovascular diseases. In these diseases, RNA-binding proteins (RBPs) have been recognized as important regulators of aberrant gene expression via post-transcriptional regulation; however, their role in PH is less clear. Identifying RBPs in PH is of great importance to better understand PH pathophysiology and to identify new targets for PH treatment. In this manuscript, we review the current knowledge on the role of dysregulated RBPs in abnormal mRNA gene expression as well as aberrant non-coding RNA processing and expression (e.g., miRNAs) in PH.

scholarly journals Determinants of RNA recognition by the FinO domain of the Escherichia coli ProQ protein

2020 ◽  
Author(s):  
Ewa M Stein ◽  
Joanna Kwiatkowska ◽  
Maciej M Basczok ◽  
Chandra M Gravel ◽  
Katherine E Berry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Small Rnas ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Rna Recognition ◽  
Rna Molecules ◽  
E Coli ◽  
Rna Ligands

Abstract The regulation of gene expression by small RNAs in Escherichia coli depends on RNA binding proteins Hfq and ProQ, which bind mostly distinct RNA pools. To understand how ProQ discriminates between RNA substrates, we compared its binding to six different RNA molecules. Full-length ProQ bound all six RNAs similarly, while the isolated N-terminal FinO domain (NTD) of ProQ specifically recognized RNAs with Rho-independent terminators. Analysis of malM 3′-UTR mutants showed that tight RNA binding by the ProQ NTD required a terminator hairpin of at least 2 bp preceding an 3′ oligoU tail of at least four uridine residues. Substitution of an A-rich sequence on the 5′ side of the terminator to uridines strengthened the binding of several ProQ-specific RNAs to the Hfq protein, but not to the ProQ NTD. Substitution of the motif in the malM-3′ and cspE-3′ RNAs also conferred the ability to bind Hfq in E. coli cells, as measured using a three-hybrid assay. In summary, these data suggest that the ProQ NTD specifically recognizes 3′ intrinsic terminators of RNA substrates, and that the discrimination between RNA ligands by E. coli ProQ and Hfq depends both on positive determinants for binding to ProQ and negative determinants against binding to Hfq.

scholarly journals Bacterial 3′UTRs: A Useful Resource in Post-transcriptional Regulation

2021 ◽  
Vol 7 ◽  
Author(s):  
Pilar Menendez-Gil ◽  
Alejandro Toledo-Arana
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Untranslated Regions ◽  
Messenger Rnas ◽  
Specific Expression ◽  
Regulate Gene Expression ◽  
Transcriptional Regulatory ◽  
Transcriptional Regulatory Mechanisms ◽  
Species Specific ◽  
Post Transcriptional Regulation

Bacterial messenger RNAs (mRNAs) are composed of 5′ and 3′ untranslated regions (UTRs) that flank the coding sequences (CDSs). In eukaryotes, 3′UTRs play key roles in post-transcriptional regulatory mechanisms. Shortening or deregulation of these regions is associated with diseases such as cancer and metabolic disorders. Comparatively, little is known about the functions of 3′UTRs in bacteria. Over the past few years, 3′UTRs have emerged as important players in the regulation of relevant bacterial processes such as virulence, iron metabolism, and biofilm formation. This MiniReview is an update for the different 3′UTR-mediated mechanisms that regulate gene expression in bacteria. Some of these include 3′UTRs that interact with the 5′UTR of the same transcript to modulate translation, 3′UTRs that are targeted by specific ribonucleases, RNA-binding proteins and small RNAs (sRNAs), and 3′UTRs that act as reservoirs of trans-acting sRNAs, among others. In addition, recent findings regarding a differential evolution of bacterial 3′UTRs and its impact in the species-specific expression of orthologous genes are also discussed.

scholarly journals In vivo discovery of RNA proximal proteins in human cells via proximity-dependent biotinylation

2020 ◽  
Author(s):  
Xianzhi Lin ◽  
Marcos A. S. Fonseca ◽  
Rosario I. Corona ◽  
Kate Lawrenson
Keyword(s):  
Gene Expression ◽  
Ascorbate Peroxidase ◽  
Genome Organization ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Structural Components ◽  
Rna Molecules ◽  
Related Proteins ◽  
Target Rna

AbstractRNA molecules function as messengers or noncoding adaptor molecules, structural components, and regulators of genome organization and gene expression. Their roles and regulation are mediated by other molecules they interact with, especially RNA binding proteins (RBPs). Here we report RNA proximity labeling (RPL), an RNA-centric method based on fusion of an endonuclease-deficient Type VI CRISPR-Cas protein (dCas13b) and engineered ascorbate peroxidase (APEX2) to discover in vivo target RNA proximal proteins (RPPs) through proximity-based biotinylation. U1 RPPs enriched by proximity-based biotinylation included both U1 snRNA canonical and noncanonical functions-related proteins. In addition, profiling of poly(A) tail proximal proteins uncovered expected categories of RBPs for poly(A) tails and also provided novel evidence for poly(A)+ RNA 5’-3’ proximity and expanded subcellular localizations. Our results suggest that RPL is a rapid approach for identifying both interacting and neighboring proteins associated with target RNA molecules in their native cellular contexts.

scholarly journals The Landscape of RNA-Protein Interactions in Plants: Approaches and Current Status

2021 ◽  
Vol 22 (6) ◽  
pp. 2845
Author(s):  
Vesper Burjoski ◽  
Anireddy S. N. Reddy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Status ◽  
Protein Coding ◽  
Rna Molecules ◽  
Cellular Processes ◽  
Binding Domains

RNAs transmit information from DNA to encode proteins that perform all cellular processes and regulate gene expression in multiple ways. From the time of synthesis to degradation, RNA molecules are associated with proteins called RNA-binding proteins (RBPs). The RBPs play diverse roles in many aspects of gene expression including pre-mRNA processing and post-transcriptional and translational regulation. In the last decade, the application of modern techniques to identify RNA–protein interactions with individual proteins, RNAs, and the whole transcriptome has led to the discovery of a hidden landscape of these interactions in plants. Global approaches such as RNA interactome capture (RIC) to identify proteins that bind protein-coding transcripts have led to the identification of close to 2000 putative RBPs in plants. Interestingly, many of these were found to be metabolic enzymes with no known canonical RNA-binding domains. Here, we review the methods used to analyze RNA–protein interactions in plants thus far and highlight the understanding of plant RNA–protein interactions these techniques have provided us. We also review some recent protein-centric, RNA-centric, and global approaches developed with non-plant systems and discuss their potential application to plants. We also provide an overview of results from classical studies of RNA–protein interaction in plants and discuss the significance of the increasingly evident ubiquity of RNA–protein interactions for the study of gene regulation and RNA biology in plants.

The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

2019 ◽  
Vol 19 (4) ◽  
pp. 255-263 ◽  
Author(s):  
Yuangang Wu ◽  
Xiaoxi Lu ◽  
Bin Shen ◽  
Yi Zeng
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Extracellular Matrix ◽  
Inflammatory Reaction ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Translation ◽  
Cochrane Library

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA. Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA. Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix. Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA. Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

scholarly journals Compendium of Methods to Uncover RNA-Protein Interactions In Vivo

2021 ◽  
Vol 4 (1) ◽  
pp. 22
Author(s):  
Mrinmoyee Majumder ◽  
Viswanathan Palanisamy
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Expression Patterns ◽  
Control Of Gene Expression ◽  
Regulatory Pathways ◽  
Advantages And Disadvantages ◽  
Protein Nucleic Acid

Control of gene expression is critical in shaping the pro-and eukaryotic organisms’ genotype and phenotype. The gene expression regulatory pathways solely rely on protein–protein and protein–nucleic acid interactions, which determine the fate of the nucleic acids. RNA–protein interactions play a significant role in co- and post-transcriptional regulation to control gene expression. RNA-binding proteins (RBPs) are a diverse group of macromolecules that bind to RNA and play an essential role in RNA biology by regulating pre-mRNA processing, maturation, nuclear transport, stability, and translation. Hence, the studies aimed at investigating RNA–protein interactions are essential to advance our knowledge in gene expression patterns associated with health and disease. Here we discuss the long-established and current technologies that are widely used to study RNA–protein interactions in vivo. We also present the advantages and disadvantages of each method discussed in the review.

scholarly journals The Interplay of RNA Binding Proteins, Oxidative Stress and Mitochondrial Dysfunction in ALS

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 552
Author(s):  
Jasmine Harley ◽  
Benjamin E. Clarke ◽  
Rickie Patani
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Mitochondrial Dysfunction ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Therapeutic Strategies ◽  
Lateral Sclerosis

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

scholarly journals The Role of RNA-Binding Proteins in Vertebrate Neural Crest and Craniofacial Development

2021 ◽  
Vol 9 (3) ◽  
pp. 34
Author(s):  
Thomas E. Forman ◽  
Brenna J. C. Dennison ◽  
Katherine A. Fantauzzo
Keyword(s):  
Gene Expression ◽  
Neural Crest ◽  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Craniofacial Development ◽  
Specific Sequence ◽  
Altered Expression ◽  
Binding Domains

Cranial neural crest (NC) cells delaminate from the neural folds in the forebrain to the hindbrain during mammalian embryogenesis and migrate into the frontonasal prominence and pharyngeal arches. These cells generate the bone and cartilage of the frontonasal skeleton, among other diverse derivatives. RNA-binding proteins (RBPs) have emerged as critical regulators of NC and craniofacial development in mammals. Conventional RBPs bind to specific sequence and/or structural motifs in a target RNA via one or more RNA-binding domains to regulate multiple aspects of RNA metabolism and ultimately affect gene expression. In this review, we discuss the roles of RBPs other than core spliceosome components during human and mouse NC and craniofacial development. Where applicable, we review data on these same RBPs from additional vertebrate species, including chicken, Xenopus and zebrafish models. Knockdown or ablation of several RBPs discussed here results in altered expression of transcripts encoding components of developmental signaling pathways, as well as reduced cell proliferation and/or increased cell death, indicating that these are common mechanisms contributing to the observed phenotypes. The study of these proteins offers a relatively untapped opportunity to provide significant insight into the mechanisms underlying gene expression regulation during craniofacial morphogenesis.

scholarly journals Coordination of RNA Processing Regulation by Signal Transduction Pathways

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1475
Author(s):  
Veronica Ruta ◽  
Vittoria Pagliarini ◽  
Claudio Sette
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Rna Processing ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Signal Transduction Pathways ◽  
Challenges And Opportunities ◽  
Common Signal

Signal transduction pathways transmit the information received from external and internal cues and generate a response that allows the cell to adapt to changes in the surrounding environment. Signaling pathways trigger rapid responses by changing the activity or localization of existing molecules, as well as long-term responses that require the activation of gene expression programs. All steps involved in the regulation of gene expression, from transcription to processing and utilization of new transcripts, are modulated by multiple signal transduction pathways. This review provides a broad overview of the post-translational regulation of factors involved in RNA processing events by signal transduction pathways, with particular focus on the regulation of pre-mRNA splicing, cleavage and polyadenylation. The effects of several post-translational modifications (i.e., sumoylation, ubiquitination, methylation, acetylation and phosphorylation) on the expression, subcellular localization, stability and affinity for RNA and protein partners of many RNA-binding proteins are highlighted. Moreover, examples of how some of the most common signal transduction pathways can modulate biological processes through changes in RNA processing regulation are illustrated. Lastly, we discuss challenges and opportunities of therapeutic approaches that correct RNA processing defects and target signaling molecules.

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