scholarly journals Searching for New Z-DNA/Z-RNA Binding Proteins Based on Structural Similarity to Experimentally Validated Zα Domain

2022 ◽  
Vol 23 (2) ◽  
pp. 768
Author(s):  
Martin Bartas ◽  
Kristyna Slychko ◽  
Václav Brázda ◽  
Jiří Červeň ◽  
Christopher A. Beaudoin ◽  
...  
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Structural Similarity ◽  
Functional Conservation ◽  
Cellular Processes ◽  
Left Handed ◽  
Replication Gene ◽  
Z Dna

Z-DNA and Z-RNA are functionally important left-handed structures of nucleic acids, which play a significant role in several molecular and biological processes including DNA replication, gene expression regulation and viral nucleic acid sensing. Most proteins that have been proven to interact with Z-DNA/Z-RNA contain the so-called Zα domain, which is structurally well conserved. To date, only eight proteins with Zα domain have been described within a few organisms (including human, mouse, Danio rerio, Trypanosoma brucei and some viruses). Therefore, this paper aimed to search for new Z-DNA/Z-RNA binding proteins in the complete PDB structures database and from the AlphaFold2 protein models. A structure-based similarity search found 14 proteins with highly similar Zα domain structure in experimentally-defined proteins and 185 proteins with a putative Zα domain using the AlphaFold2 models. Structure-based alignment and molecular docking confirmed high functional conservation of amino acids involved in Z-DNA/Z-RNA, suggesting that Z-DNA/Z-RNA recognition may play an important role in a variety of cellular processes.

scholarly journals Transcription Is Just the Beginning of Gene Expression Regulation: The Functional Significance of RNA-Binding Proteins to Post-transcriptional Processes in Plants

2019 ◽  
Vol 60 (9) ◽  
pp. 1939-1952 ◽  
Author(s):  
Wil Prall ◽  
Bishwas Sharma ◽  
Brian D Gregory
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Global Climate ◽  
Genome Mining ◽  
Valuable Insight ◽  
Cellular Processes ◽  
High Level ◽  
And Function

Abstract Plants have developed sophisticated mechanisms to compensate and respond to ever-changing environmental conditions. Research focus in this area has recently shifted towards understanding the post-transcriptional mechanisms that contribute to RNA transcript maturation, abundance and function as key regulatory steps in allowing plants to properly react and adapt to these never-ending shifts in their environments. At the center of these regulatory mechanisms are RNA-binding proteins (RBPs), the functional mediators of all post-transcriptional processes. In plants, RBPs are becoming increasingly appreciated as the critical modulators of core cellular processes during development and in response to environmental stimuli. With the majority of research on RBPs and their functions historically in prokaryotic and mammalian systems, it has more recently been unveiled that plants have expanded families of conserved and novel RBPs compared with their eukaryotic counterparts. To better understand the scope of RBPs in plants, we present past and current literature detailing specific roles of RBPs during stress response, development and other fundamental transition periods. In this review, we highlight examples of complex regulation coordinated by RBPs with a focus on the diverse mechanisms of plant RBPs and the unique processes they regulate. Additionally, we discuss the importance for additional research into understanding global interactions of RBPs on a systems and network-scale, with genome mining and annotation providing valuable insight for potential uses in improving crop plants in order to maintain high-level production in this era of global climate change.

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 A Deep Boosting Based Approach for Capturing the Sequence Binding Preferences of RNA-Binding Proteins from High-Throughput CLIP-Seq Data

2016 ◽  
Author(s):  
Shuya Li ◽  
Fanghong Dong ◽  
Yuexin Wu ◽  
Sai Zhang ◽  
Chen Zhang ◽  
...  
Keyword(s):  
High Throughput ◽  
Large Scale ◽  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
False Negative ◽  
Functional Roles ◽  
Potential Applications ◽  
Validation Tests

AbstractCharacterizing the binding behaviors of RNA-binding proteins (RBPs) is important for understanding their functional roles in gene expression regulation. However, current high-throughput experimental methods for identifying RBP targets, such as CLIP-seq and RNAcompete, usually suffer from the false positive and false negative issues. Here, we develop a deep boosting based machine learning approach, called DeBooster, to accurately model the binding sequence preferences and identify the corresponding binding targets of RBPs from CLIP-seq data. Comprehensive validation tests have shown that DeBooster can outperform other state-of-the-art approaches in predicting RBP targets and recover false negatives that are common in current CLIP-seq data. In addition, we have demonstrated several new potential applications of DeBooster in understanding the regulatory functions of RBPs, including the binding effects of the RNA helicase MOV10 on mRNA degradation, the influence of different binding behaviors of the ADAR proteins on RNA editing, as well as the antagonizing effect of RBP binding on miRNA repression. Moreover, DeBooster may provide an effective index to investigate the effect of pathogenic mutations in RBP binding sites, especially those related to splicing events. We expect that DeBooster will be widely applied to analyze large-scale CLIP-seq experimental data and can provide a practically useful tool for novel biological discoveries in understanding the regulatory mechanisms of RBPs.

scholarly journals RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6835
Author(s):  
Jonas Weiße ◽  
Julia Rosemann ◽  
Vanessa Krauspe ◽  
Matthias Kappler ◽  
Alexander W. Eckert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Invasion And Metastasis ◽  
Protein Coding ◽  
Oral Cancers ◽  
Cellular Processes ◽  
Post Transcriptional Regulation

Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.

scholarly journals Functional Roles of RNA-Binding Proteins in Plant Signaling

Life ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 288
Author(s):  
Victor Muleya ◽  
Claudius Marondedze
Keyword(s):  
Stress Responses ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Structural Similarity ◽  
Plant Signaling ◽  
Affinity Capture ◽  
Functional Roles ◽  
Binding Domains ◽  
Mrna Targets

RNA-binding proteins (RBPs) are typical proteins that bind RNA through single or multiple RNA-binding domains (RBDs). These proteins have a functional role in determining the fate or function of the bound RNAs. A few hundred RBPs were known through in silico prediction based on computational assignment informed by structural similarity and the presence of classical RBDs. However, RBPs lacking such conventional RBDs were omitted. Owing to the recent mRNA interactome capture technology based on UV-crosslinking and fixing proteins to their mRNA targets followed by affinity capture purification and identification of RBPs by tandem mass spectrometry, several hundreds of RBPs have recently been discovered. These proteome-wide studies have colossally increased the number of proteins implicated in RNA binding and unearthed hundreds of novel RBPs lacking classical RBDs, such as proteins involved in intermediary metabolism. These discoveries provide wide insights into the post-transcriptional gene regulation players and their role in plant signaling, such as environmental stress conditions. In this review, novel discoveries of RBPs are explored, particularly on the evolving knowledge of their role in stress responses. The molecular functions of these RBPs, particularly focusing on those that do not have classical RBDs, are also elucidated at the systems level.

scholarly journals RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

2020 ◽  
Vol 21 (8) ◽  
pp. 2969 ◽  
Author(s):  
Katharina Jonas ◽  
George A. Calin ◽  
Martin Pichler
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Stability ◽  
Protein Coding ◽  
Cellular Processes ◽  
Open Questions ◽  
Non Coding Rnas ◽  
The Stability ◽  
Mrna Binding

The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments.

Deciphering the architecture and interactome of hnRNP proteins

2021 ◽  
Author(s):  
Helisa H Wippel ◽  
Mariana Fioramonte ◽  
Juan D Chavez ◽  
James E Bruce
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Conserved Domains ◽  
Consensus Sequences ◽  
Cellular Processes ◽  
Hnrnp Proteins

RNA-binding proteins (RBPs) have conserved domains and consensus sequences that interact with RNAs and other proteins forming ribonucleoprotein (RNP) complexes. RNPs are involved in the regulation of several cellular processes,...

scholarly journals RBP2GO: a comprehensive pan-species database on RNA-binding proteins, their interactions and functions

2020 ◽  
Vol 49 (D1) ◽  
pp. D425-D436 ◽  
Author(s):  
Maiwen Caudron-Herger ◽  
Ralf E Jansen ◽  
Elsa Wassmer ◽  
Sven Diederichs
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Protein Complexes ◽  
Rapid Evolution ◽  
Cellular Processes ◽  
Advanced Search ◽  
New Research ◽  
Cellular Compartments ◽  
User Friendly

Abstract RNA–protein complexes have emerged as central players in numerous key cellular processes with significant relevance in health and disease. To further deepen our knowledge of RNA-binding proteins (RBPs), multiple proteome-wide strategies have been developed to identify RBPs in different species leading to a large number of studies contributing experimentally identified as well as predicted RBP candidate catalogs. However, the rapid evolution of the field led to an accumulation of isolated datasets, hampering the access and comparison of their valuable content. Moreover, tools to link RBPs to cellular pathways and functions were lacking. Here, to facilitate the efficient screening of the RBP resources, we provide RBP2GO (https://RBP2GO.DKFZ.de), a comprehensive database of all currently available proteome-wide datasets for RBPs across 13 species from 53 studies including 105 datasets identifying altogether 22 552 RBP candidates. These are combined with the information on RBP interaction partners and on the related biological processes, molecular functions and cellular compartments. RBP2GO offers a user-friendly web interface with an RBP scoring system and powerful advanced search tools allowing forward and reverse searches connecting functions and RBPs to stimulate new research directions.

eIF4E-binding proteins: new factors, new locations, new roles

2014 ◽  
Vol 42 (4) ◽  
pp. 1238-1245 ◽  
Author(s):  
Anastasiia Kamenska ◽  
Clare Simpson ◽  
Nancy Standart
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Ribosomal Subunit ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor 4E ◽  
New Locations ◽  
Specific Mrnas

The cap-binding translation initiation factor eIF4E (eukaryotic initiation factor 4E) is central to protein synthesis in eukaryotes. As an integral component of eIF4F, a complex also containing the large bridging factor eIF4G and eIF4A RNA helicase, eIF4E enables the recruitment of the small ribosomal subunit to the 5′ end of mRNAs. The interaction between eIF4E and eIF4G via a YXXXXLϕ motif is regulated by small eIF4E-binding proteins, 4E-BPs, which use the same sequence to competitively bind eIF4E thereby inhibiting cap-dependent translation. Additional eIF4E-binding proteins have been identified in the last 10–15 years, characterized by the YXXXXLϕ motif, and by interactions (many of which remain to be detailed) with RNA-binding proteins, or other factors in complexes that recognize the specific mRNAs. In the present article, we focus on the metazoan 4E-T (4E-transporter)/Cup family of eIF4E-binding proteins, and also discuss very recent examples in yeast, fruitflies and humans, some of which predictably inhibit translation, while others may result in mRNA decay or even enhance translation; altogether considerably expanding our understanding of the roles of eIF4E-binding proteins in gene expression regulation.

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