scholarly journals The devil is in the domain: understanding protein recognition of multiple RNA targets

2017 ◽  
Vol 45 (6) ◽  
pp. 1305-1311 ◽  
Author(s):  
Glen R. Gronland ◽  
Andres Ramos
Keyword(s):  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Rna Regulation ◽  
Control Of Gene Expression ◽  
Binding Domains ◽  
Large Sets ◽  
Rna Targets ◽  
And Function ◽  
The Devil

RNA regulation provides a finely tuned and highly co-ordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on a recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. Deconvoluting the molecular complexity of the RNA regulatory network is essential to understanding cell differentiation and function, and requires accurate models for protein–RNA recognition and protein target selectivity. We discuss that the structural and molecular understanding of the key determinant of recognition, together with the availability of methods to examine protein–RNA interactions at the transcriptome level, may provide an avenue to establish these models.

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 POLIII-derived non-coding RNAs acting as scaffolds and decoys

2019 ◽  
Vol 11 (10) ◽  
pp. 880-885 ◽  
Author(s):  
Hendrik Täuber ◽  
Stefan Hüttelmaier ◽  
Marcel Köhn
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Cellular Functions ◽  
Control Of Gene Expression ◽  
Ribonucleoprotein Complexes ◽  
Small Ncrnas ◽  
Non Coding Rnas ◽  
And Function

Abstract A large variety of eukaryotic small structured POLIII-derived non-coding RNAs (ncRNAs) have been described in the past. However, for only few, e.g. 7SL and H1/MRP families, cellular functions are well understood. For the vast majority of these transcripts, cellular functions remain unknown. Recent findings on the role of Y RNAs and other POLIII-derived ncRNAs suggest an evolutionarily conserved function of these ncRNAs in the assembly and function of ribonucleoprotein complexes (RNPs). These RNPs provide cellular `machineries’, which are essential for guiding the fate and function of a variety of RNAs. In this review, we summarize current knowledge on the role of POLIII-derived ncRNAs in the assembly and function of RNPs. We propose that these ncRNAs serve as scaffolding factors that `chaperone’ RNA-binding proteins (RBPs) to form functional RNPs. In addition or associated with this role, some small ncRNAs act as molecular decoys impairing the RBP-guided control of RNA fate by competing with other RNA substrates. This suggests that POLIII-derived ncRNAs serve essential and conserved roles in the assembly of larger RNPs and thus the control of gene expression by indirectly guiding the fate of mRNAs and lncRNAs.

scholarly journals Long Non-Coding RNA-Ribonucleoprotein Networks in the Post-Transcriptional Control of Gene Expression

2020 ◽  
Vol 6 (3) ◽  
pp. 40
Author(s):  
Paola Briata ◽  
Roberto Gherzi
Keyword(s):  
Transcriptional Control ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Huge Number ◽  
Protein Coding ◽  
Control Of Gene Expression ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
And Function ◽  
Long Non Coding Rna

Although mammals possess roughly the same number of protein-coding genes as worms, it is evident that the non-coding transcriptome content has become far broader and more sophisticated during evolution. Indeed, the vital regulatory importance of both short and long non-coding RNAs (lncRNAs) has been demonstrated during the last two decades. RNA binding proteins (RBPs) represent approximately 7.5% of all proteins and regulate the fate and function of a huge number of transcripts thus contributing to ensure cellular homeostasis. Transcriptomic and proteomic studies revealed that RBP-based complexes often include lncRNAs. This review will describe examples of how lncRNA-RBP networks can virtually control all the post-transcriptional events in the cell.

scholarly journals Regulation and Function of RNA Pseudouridylation in Human Cells

2020 ◽  
Vol 54 (1) ◽  
pp. 309-336
Author(s):  
Erin K. Borchardt ◽  
Nicole M. Martinez ◽  
Wendy V. Gilbert
Keyword(s):  
Messenger Rna ◽  
Noncoding Rna ◽  
Protein Production ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Human Cells ◽  
Rna Sequences ◽  
Rna Targets ◽  
Pseudouridine Synthases ◽  
And Function

Recent advances in pseudouridine detection reveal a complex pseudouridine landscape that includes messenger RNA and diverse classes of noncoding RNA in human cells. The known molecular functions of pseudouridine, which include stabilizing RNA conformations and destabilizing interactions with varied RNA-binding proteins, suggest that RNA pseudouridylation could have widespread effects on RNA metabolism and gene expression. Here, we emphasize how much remains to be learned about the RNA targets of human pseudouridine synthases, their basis for recognizing distinct RNA sequences, and the mechanisms responsible for regulated RNA pseudouridylation. We also examine the roles of noncoding RNA pseudouridylation in splicing and translation and point out the potential effects of mRNA pseudouridylation on protein production, including in the context of therapeutic mRNAs.

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 A Live-Cell Assay for the Detection of pre-microRNA-Protein Interactions

2020 ◽  
Author(s):  
Sydney L. Rosenblum ◽  
Daniel A. Lorenz ◽  
Amanda L. Garner
Keyword(s):  
Protein Interactions ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Live Cell ◽  
Cell Detection ◽  
Binding Domains ◽  
Genome Wide ◽  
Rna Interaction ◽  
And Function ◽  
Specific Sequences

AbstractRecent efforts in genome-wide sequencing and proteomics have revealed the fundamental roles that RNA-binding proteins (RBPs) play in the life cycle and function of both coding and non-coding RNAs. While these methodologies provide a systems-level view of the networking of RNA and proteins, approaches to enable the cellular validation of discovered interactions are lacking. Leveraging the power of bioorthogonal chemistry- and split-luciferase-based assay technologies, we have devised a conceptually new assay for the live-cell detection of RNA-protein interactions (RPIs), RNA interaction with Protein-mediated Complementation Assay, or RiPCA. As proof-of-concept, we have utilized the interaction of the pre-microRNA, pre-let-7, with its binding partner, Lin28. Using this system, we have demonstrated the selective detection of the pre-let-7-Lin28 RPI in both the cytoplasm and nucleus. Furthermore, we determined this technology can be used to discern relative affinities for specific sequences as well as of individual RNA binding domains. Thus, RiPCA has the potential to serve as a useful tool in supporting the investigation of cellular RPIs.

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 A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4

2021 ◽  
Author(s):  
Christoph Sadee ◽  
Lauren Hagler ◽  
Winston Becker ◽  
Inga Jarmoskaite ◽  
Pavanapuresan Vaidyanathan ◽  
...  
Keyword(s):  
Thermodynamic Model ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Cellular Interactions ◽  
Base Flipping ◽  
Cellular Models ◽  
Rna Targets ◽  
Binding Data ◽  
Direct Binding ◽  
And Function

Abstract Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a complete thermodynamic model for RNA binding to the S. cerevisiae Pumilio protein PUF4 derived from direct binding data for 6180 RNAs measured using the RNA on a massively parallel array (RNA-MaP) platform. The PUF4 model is highly similar to that of the related RBPs, human PUM2 and PUM1, with one marked exception: a single favorable site of base flipping for PUF4, such that PUF4 preferentially binds to a non-contiguous series of residues. These results are foundational for developing and testing cellular models of RNA-RBP interactions and function, for engineering RBPs, for understanding the biophysical nature of RBP binding and the evolutionary landscape of RNAs and RBPs.

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 Emerging Roles of the RNA Binding Protein QKI in Cardiovascular Development and Function

2021 ◽  
Vol 9 ◽  
Author(s):  
Xinyun Chen ◽  
Jianwen Yin ◽  
Dayan Cao ◽  
Deyong Xiao ◽  
Zhongjun Zhou ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Property ◽  
Cardiovascular Development ◽  
Potential Link ◽  
Alternatively Spliced ◽  
Unique Cell ◽  
Carboxy Terminal ◽  
And Function

RNA binding proteins (RBPs) have a broad biological and physiological function and are critical in regulating pre-mRNA posttranscriptional processing, intracellular migration, and mRNA stability. QKI, also known as Quaking, is a member of the signal transduction and activation of RNA (STAR) family, which also belongs to the heterogeneous nuclear ribonucleoprotein K- (hnRNP K-) homology domain protein family. There are three major alternatively spliced isoforms, QKI-5, QKI-6, and QKI-7, differing in carboxy-terminal domains. They share a common RNA binding property, but each isoform can regulate pre-mRNA splicing, transportation or stability differently in a unique cell type-specific manner. Previously, QKI has been known for its important role in contributing to neurological disorders. A series of recent work has further demonstrated that QKI has important roles in much broader biological systems, such as cardiovascular development, monocyte to macrophage differentiation, bone metabolism, and cancer progression. In this mini-review, we will focus on discussing the emerging roles of QKI in regulating cardiac and vascular development and function and its potential link to cardiovascular pathophysiology.

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