scholarly journals Abstract P-22: Enhanced Crosslinking and Immunoprecipitation (Eclip) Data Reveal Interactions of RNA Binding Proteins with the Human Ribosome

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S21-S21
Author(s):  
Andrey Buyan ◽  
Ivan Kulakovskiy ◽  
Sergey Dmitriev
Keyword(s):  
Translational Control ◽  
Nuclear Export ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Repetitive Sequences ◽  
Structural Data

Background: The ribosome is a protein-synthesizing molecular machine composed of four ribosomal RNAs (rRNAs) and dozens of ribosomal proteins. In mammals, the ribosome has a complicated structure with an additional outer layer of rRNA, including large tentacle-like extensions. A number of RNA binding proteins (RBPs) interact with this layer to assist ribosome biogenesis, nuclear export and decay, or to modulate translation. Plenty of methods have been developed in the last decade in order to study such protein-RNA interactions, including RNA pulldown and crosslinking-immunoprecipitation (CLIP) assays. Methods: In the current study, using publicly available data of the enhanced CLIP (eCLIP) experiments for 223 proteins studied in the ENCODE project, we found a number of RBPs that bind rRNAs in human cells. To locate their binding sites in rRNAs, we used a newly developed computational protocol for mapping and evaluation of the eCLIP data with the respect to the repetitive sequences. Results: For two proteins with known ribosomal localization, uS3/RPS3 and uS17/RPS11, the identified sites were in good agreement with structural data, thus validating our approach. Then, we identified rRNA contacts of overall 22 RBPs involved in rRNA processing and ribosome maturation (DDX21, DDX51, DDX52, NIP7, SBDS, UTP18, UTP3, WDR3, and WDR43), translational control during stress (SERBP1, G3BP1, SND1), IRES activity (PCBP1/hnRNPE1), and other translation-related functions. In many cases, the identified proteins interact with the rRNA expansion segments (ES) of the human ribosome pointing to their important role in protein synthesis. Conclusion: Our study identifies a number of RBPs as interacting partners of the human ribosome and sheds light on the role of rRNA expansion segments in translation.

scholarly journals Expanding Role of Ubiquitin in Translational Control

2020 ◽  
Vol 21 (3) ◽  
pp. 1151 ◽  
Author(s):  
Shannon E. Dougherty ◽  
Austin O. Maduka ◽  
Toshifumi Inada ◽  
Gustavo M. Silva
Keyword(s):  
Translational Control ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Rna Binding ◽  
Protein Quality ◽  
Rna Binding Proteins ◽  
Ubiquitin Chain ◽  
Molecular Aspects ◽  
And Function

The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.

scholarly journals Emerging Roles of RNA-Binding Proteins in Seed Development and Performance

2020 ◽  
Vol 21 (18) ◽  
pp. 6822
Author(s):  
Lijuan Lou ◽  
Ling Ding ◽  
Tao Wang ◽  
Yong Xiang
Keyword(s):  
Seed Development ◽  
Translational Control ◽  
Nuclear Export ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Research Progress ◽  
Mrna Metabolism ◽  
And Performance ◽  
Post Transcriptional Regulation

Seed development, dormancy, and germination are key physiological events that are not only important for seed generation, survival, and dispersal, but also contribute to agricultural production. RNA-binding proteins (RBPs) directly interact with target mRNAs and fine-tune mRNA metabolism by governing post-transcriptional regulation, including RNA processing, intron splicing, nuclear export, trafficking, stability/decay, and translational control. Recent studies have functionally characterized increasing numbers of diverse RBPs and shown that they participate in seed development and performance, providing significant insight into the role of RBP–mRNA interactions in seed processes. In this review, we discuss recent research progress on newly defined RBPs that have crucial roles in RNA metabolism and affect seed development, dormancy, and germination.

Translational control mechanisms in metabolic regulation: critical role of RNA binding proteins, microRNAs, and cytoplasmic RNA granules

2011 ◽  
Vol 301 (6) ◽  
pp. E1051-E1064 ◽  
Author(s):  
Khosrow Adeli
Keyword(s):  
Protein Synthesis ◽  
Translational Control ◽  
Metabolic Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Critical Role ◽  
Mrna Translation ◽  
Rna Granules

Regulated cell metabolism involves acute and chronic regulation of gene expression by various nutritional and endocrine stimuli. To respond effectively to endogenous and exogenous signals, cells require rapid response mechanisms to modulate transcript expression and protein synthesis and cannot, in most cases, rely on control of transcriptional initiation that requires hours to take effect. Thus, co- and posttranslational mechanisms have been increasingly recognized as key modulators of metabolic function. This review highlights the critical role of mRNA translational control in modulation of global protein synthesis as well as specific protein factors that regulate metabolic function. First, the complex lifecycle of eukaryotic mRNAs will be reviewed, including our current understanding of translational control mechanisms, regulation by RNA binding proteins and microRNAs, and the role of RNA granules, including processing bodies and stress granules. Second, the current evidence linking regulation of mRNA translation with normal physiological and metabolic pathways and the associated disease states are reviewed. A growing body of evidence supports a key role of translational control in metabolic regulation and implicates translational mechanisms in the pathogenesis of metabolic disorders such as type 2 diabetes. The review also highlights translational control of apolipoprotein B (apoB) mRNA by insulin as a clear example of endocrine modulation of mRNA translation to bring about changes in specific metabolic pathways. Recent findings made on the role of 5′-untranslated regions (5′-UTR), 3′-UTR, RNA binding proteins, and RNA granules in mediating insulin regulation of apoB mRNA translation, apoB protein synthesis, and hepatic lipoprotein production are discussed.

DT-03-02: Viewing neurodegeneration beyond the tangle: The role of RNA binding proteins in Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P847-P847
Author(s):  
Benjamin Wolozin ◽  
Tara Vanderweyde ◽  
Liqun Liu-Yesucevitz ◽  
Alpaslan Dedeoglu ◽  
Leonard Petrucelli ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

scholarly journals RNA-binding proteins of the NXF (nuclear export factor) family and their connection with the cytoskeleton

Cytoskeleton ◽  
2017 ◽  
Vol 74 (4) ◽  
pp. 161-169 ◽  
Author(s):  
L. A. Mamon ◽  
V. R. Ginanova ◽  
S. F. Kliver ◽  
A. O. Yakimova ◽  
A. A. Atsapkina ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

scholarly journals Matrin3: Disorder and ALS Pathogenesis

2022 ◽  
Vol 8 ◽  
Author(s):  
Ahmed Salem ◽  
Carter J. Wilson ◽  
Benjamin S. Rutledge ◽  
Allison Dilliott ◽  
Sali Farhan ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Binding Proteins ◽  
Rna Binding ◽  
Nuclear Dna ◽  
Neurodegenerative Disorder ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions ◽  
Disordered Regions

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the degeneration of both upper and lower motor neurons in the brain and spinal cord. ALS is associated with protein misfolding and inclusion formation involving RNA-binding proteins, including TAR DNA-binding protein (TDP-43) and fused in sarcoma (FUS). The 125-kDa Matrin3 is a highly conserved nuclear DNA/RNA-binding protein that is implicated in many cellular processes, including binding and stabilizing mRNA, regulating mRNA nuclear export, modulating alternative splicing, and managing chromosomal distribution. Mutations in MATR3, the gene encoding Matrin3, have been identified as causal in familial ALS (fALS). Matrin3 lacks a prion-like domain that characterizes many other ALS-associated RNA-binding proteins, including TDP-43 and FUS, however, our bioinformatics analyses and preliminary studies document that Matrin3 contains long intrinsically disordered regions that may facilitate promiscuous interactions with many proteins and may contribute to its misfolding. In addition, these disordered regions in Matrin3 undergo numerous post-translational modifications, including phosphorylation, ubiquitination and acetylation that modulate the function and misfolding of the protein. Here we discuss the disordered nature of Matrin3 and review the factors that may promote its misfolding and aggregation, two elements that might explain its role in ALS pathogenesis.

scholarly journals RNA Is a Double-Edged Sword in ALS Pathogenesis

2021 ◽  
Vol 15 ◽  
Author(s):  
Benjamin L. Zaepfel ◽  
Jeffrey D. Rothstein
Keyword(s):  
Motor Neurons ◽  
Cortical Neurons ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Metabolism ◽  
Small Subset ◽  
Toxic Rna ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease that affects upper and lower motor neurons. Familial ALS accounts for a small subset of cases (<10–15%) and is caused by dominant mutations in one of more than 10 known genes. Multiple genes have been causally or pathologically linked to both ALS and frontotemporal dementia (FTD). Many of these genes encode RNA-binding proteins, so the role of dysregulated RNA metabolism in neurodegeneration is being actively investigated. In addition to defects in RNA metabolism, recent studies provide emerging evidence into how RNA itself can contribute to the degeneration of both motor and cortical neurons. In this review, we discuss the roles of altered RNA metabolism and RNA-mediated toxicity in the context of TARDBP, FUS, and C9ORF72 mutations. Specifically, we focus on recent studies that describe toxic RNA as the potential initiator of disease, disease-associated defects in specific RNA metabolism pathways, as well as how RNA-based approaches can be used as potential therapies. Altogether, we highlight the importance of RNA-based investigations into the molecular progression of ALS, as well as the need for RNA-dependent structural studies of disease-linked RNA-binding proteins to identify clear therapeutic targets.

The Expanding Role of RNA-Binding Proteins in Neurodegeneration

2019 ◽  
pp. 373-403
Author(s):  
Bhawana Maurya ◽  
Satya Surabhi ◽  
Pranjali Pandey ◽  
Ashim Mukherjee ◽  
Mousumi Mutsuddi
Keyword(s):  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins

scholarly journals Roles of Organellar RNA-Binding Proteins in Plant Growth, Development, and Abiotic Stress Responses

2020 ◽  
Vol 21 (12) ◽  
pp. 4548 ◽  
Author(s):  
Kwanuk Lee ◽  
Hunseung Kang
Keyword(s):  
Abiotic Stress ◽  
Plant Growth ◽  
Stress Responses ◽  
Translational Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Metabolism ◽  
Functional Roles ◽  
Growth Development

Organellar gene expression (OGE) in chloroplasts and mitochondria is primarily modulated at post-transcriptional levels, including RNA processing, intron splicing, RNA stability, editing, and translational control. Nucleus-encoded Chloroplast or Mitochondrial RNA-Binding Proteins (nCMRBPs) are key regulatory factors that are crucial for the fine-tuned regulation of post-transcriptional RNA metabolism in organelles. Although the functional roles of nCMRBPs have been studied in plants, their cellular and physiological functions remain largely unknown. Nevertheless, existing studies that have characterized the functions of nCMRBP families, such as chloroplast ribosome maturation and splicing domain (CRM) proteins, pentatricopeptide repeat (PPR) proteins, DEAD-Box RNA helicase (DBRH) proteins, and S1-domain containing proteins (SDPs), have begun to shed light on the role of nCMRBPs in plant growth, development, and stress responses. Here, we review the latest research developments regarding the functional roles of organellar RBPs in RNA metabolism during growth, development, and abiotic stress responses in plants.

Sign in / Sign up

Export Citation Format

Share Document