scholarly journals Autophagy Regulation by Crosstalk between miRNAs and Ubiquitination System

2021 ◽  
Vol 22 (21) ◽  
pp. 11912
Author(s):  
Junyan Qu ◽  
Zhenghong Lin
Keyword(s):  
Direct Interaction ◽  
Decisive Role ◽  
Ubiquitin Ligases ◽  
Eukaryotic Cells ◽  
Biological Processes ◽  
E3 Ubiquitin Ligases ◽  
Post Translational Modifications ◽  
Rna Molecules ◽  
Endogenous Genes ◽  
Ubiquitination System

MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes with ~22 nucleotides which are involved in the regulation of post-transcriptional gene expression. Ubiquitination and deubiquitination are common post-translational modifications in eukaryotic cells and important pathways in regulating protein degradation and signal transduction, in which E3 ubiquitin ligases and deubiquitinases (DUBs) play a decisive role. MiRNA and ubiquitination are involved in the regulation of most biological processes, including autophagy. Furthermore, in recent years, the direct interaction between miRNA and E3 ubiquitin ligases or deubiquitinases has attracted much attention, and the cross-talk between miRNA and ubiquitination system has been proved to play key regulatory roles in a variety of diseases. In this review, we summarized the advances in autophagy regulation by crosstalk between miRNA and E3 ubiquitin ligases or deubiquitinases.

scholarly journals Circulating MicroRNAs as Potential Molecular Biomarkers in Pathophysiological Evolution of Pregnancy

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Dragos Cretoiu ◽  
Jiahong Xu ◽  
Junjie Xiao ◽  
Nicolae Suciu ◽  
Sanda Maria Cretoiu
Keyword(s):  
Small Rna ◽  
Eukaryotic Cells ◽  
Biological Processes ◽  
Recurrent Abortion ◽  
Circulating Mirnas ◽  
Circulating Micrornas ◽  
Rna Molecules ◽  
Potential Value ◽  
Pregnancy Status ◽  
Implantation Period

MicroRNAs represent nonprotein coding small RNA molecules that are very stable to degradation and responsible for gene silencing in most eukaryotic cells. Increased evidence has been accumulating over the years about their potential value as biomarkers for several diseases. MicroRNAs were predicted to be involved in nearly all biological processes from development to oncogenesis. In this review, we address the importance of circulating microRNAs in different conditions associated with pregnancy starting with the implantation period to preeclampsia and we shortly describe the correlation between placental circulating miRNAs and pregnancy status. We also discuss the importance of microRNAs in recurrent abortion and ectopic pregnancy.

scholarly journals Regulation of E3 ubiquitin ligases by homotypic and heterotypic assembly

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 88 ◽  
Author(s):  
Vishnu Balaji ◽  
Thorsten Hoppe
Keyword(s):  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Substrate Selection ◽  
Post Translational Modifications ◽  
E3 Ligases ◽  
Physiological Conditions ◽  
P Protein ◽  
Heterotypic Interactions ◽  
Enzymatic Machinery ◽  
Substrate Proteins

Protein ubiquitylation is essential for the maintenance of cellular homeostasis. E3 ubiquitin ligases are key components of the enzymatic machinery catalyzing the attachment of ubiquitin to substrate proteins. Consequently, enzymatic dysfunction has been associated with medical conditions including cancer, diabetes, and cardiovascular and neurodegenerative disorders. To safeguard substrate selection and ubiquitylation, the activity of E3 ligases is tightly regulated by post-translational modifications including phosphorylation, sumoylation, and ubiquitylation, as well as binding of alternative adaptor molecules and cofactors. Recent structural studies identified homotypic and heterotypic interactions between E3 ligases, adding another layer of control for rapid adaptation to changing environmental and physiological conditions. Here, we discuss the regulation of E3 ligase activity by combinatorial oligomerization and summarize examples of associated ubiquitylation pathways and mechanisms.

scholarly journals A Decoy Library Uncovers U-box E3 Ubiquitin Ligases that Regulate Flowering Time in Arabidopsis

2020 ◽  
Author(s):  
Ann M. Feke ◽  
Jing Hong ◽  
Wei Liu ◽  
Joshua M. Gendron
Keyword(s):  
Flowering Time ◽  
Ubiquitin Ligase ◽  
Floral Development ◽  
E3 Ubiquitin Ligase ◽  
Development Program ◽  
Ubiquitin Ligases ◽  
Biological Processes ◽  
E3 Ubiquitin Ligases ◽  
Developmental Transitions ◽  
Bona Fide

ABSTRACTTargeted degradation of proteins is mediated by E3 ubiquitin ligases and is important for the execution of many biological processes. Previously, we created and employed a large library of E3 ubiquitin ligase decoys to identify regulators of the circadian clock (Feke et al., 2019). In tandem with the screen for circadian regulators, we performed a flowering time screen using our U-box-type E3 ubiquitin ligase decoy transgenic library. We identified five U-box decoy transgenic populations that have defects in flowering time or the floral development program. We used additional genetic and biochemical studies to validate PLANT U-BOX 14 (PUB14), MOS4-ASSOCIATED COMPLEX 3A (MAC3A), and MAC3B as bona fide regulators of flowering time. This work reinforces the utility of the decoy library in identifying regulators of important developmental transitions in plants and expands the scope of the technique beyond our previous studies.

scholarly journals The Role of E3 Ubiquitin Ligases and Deubiquitinases in Inflammatory Bowel Disease: Friend or Foe?

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Zou ◽  
Qi-Shan Zeng ◽  
Jiao Nie ◽  
Jia-Hui Yang ◽  
Zhen-Yi Luo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Cell Cycle Progression ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Immune Disorder ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), exhibits a complex multifactorial pathogenesis involving genetic susceptibility, imbalance of gut microbiota, mucosal immune disorder and environmental factors. Recent studies reported associations between ubiquitination and deubiquitination and the occurrence and development of inflammatory bowel disease. Ubiquitination modification, one of the most important types of post-translational modifications, is a multi-step enzymatic process involved in the regulation of various physiological processes of cells, including cell cycle progression, cell differentiation, apoptosis, and innate and adaptive immune responses. Alterations in ubiquitination and deubiquitination can lead to various diseases, including IBD. Here, we review the role of E3 ubiquitin ligases and deubiquitinases (DUBs) and their mediated ubiquitination and deubiquitination modifications in the pathogenesis of IBD. We highlight the importance of this type of posttranslational modification in the development of inflammation, and provide guidance for the future development of targeted therapeutics in IBD.

Regulation of Epithelial-Mesenchymal Transition by E3 Ubiquitin Ligases and Deubiquitinase in Cancer

2016 ◽  
Vol 16 (2) ◽  
pp. 110-118 ◽  
Author(s):  
Yasumichi Inoue ◽  
Yuka Itoh ◽  
Koichi Sato ◽  
Fumihiro Kawasaki ◽  
Chihiro Sumita ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Mesenchymal Transition

scholarly journals Structural relation matching: an algorithm to identify structural patterns into RNAs and their interactions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michela Quadrini
Keyword(s):  
Hydrogen Bonding ◽  
Secondary Structure ◽  
Nucleotide Sequence ◽  
Thermus Thermophilus ◽  
Three Dimensional ◽  
Secondary Structures ◽  
Structural Effect ◽  
Biological Processes ◽  
Structural Pattern ◽  
Rna Molecules

Abstract RNA molecules play crucial roles in various biological processes. Their three-dimensional configurations determine the functions and, in turn, influences the interaction with other molecules. RNAs and their interaction structures, the so-called RNA–RNA interactions, can be abstracted in terms of secondary structures, i.e., a list of the nucleotide bases paired by hydrogen bonding within its nucleotide sequence. Each secondary structure, in turn, can be abstracted into cores and shadows. Both are determined by collapsing nucleotides and arcs properly. We formalize all of these abstractions as arc diagrams, whose arcs determine loops. A secondary structure, represented by an arc diagram, is pseudoknot-free if its arc diagram does not present any crossing among arcs otherwise, it is said pseudoknotted. In this study, we face the problem of identifying a given structural pattern into secondary structures or the associated cores or shadow of both RNAs and RNA–RNA interactions, characterized by arbitrary pseudoknots. These abstractions are mapped into a matrix, whose elements represent the relations among loops. Therefore, we face the problem of taking advantage of matrices and submatrices. The algorithms, implemented in Python, work in polynomial time. We test our approach on a set of 16S ribosomal RNAs with inhibitors of Thermus thermophilus, and we quantify the structural effect of the inhibitors.

scholarly journals Ubiquitination, Biotech Startups, and the Future of TRIM Family Proteins: A TRIM-Endous Opportunity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1015
Author(s):  
Utsa Bhaduri ◽  
Giuseppe Merla
Keyword(s):  
Drug Discovery ◽  
Protein Degradation ◽  
Ubiquitin Ligase ◽  
Genetic Disorders ◽  
E3 Ubiquitin Ligase ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Post Translational Modification ◽  
Disease Biology ◽  
The Future

Ubiquitination is a post-translational modification that has pivotal roles in protein degradation and diversified cellular processes, and for more than two decades it has been a subject of interest in the biotech or biopharmaceutical industry. Tripartite motif (TRIM) family proteins are known to have proven E3 ubiquitin ligase activities and are involved in a multitude of cellular and physiological events and pathophysiological conditions ranging from cancers to rare genetic disorders. Although in recent years many kinds of E3 ubiquitin ligases have emerged as the preferred choices of big pharma and biotech startups in the context of protein degradation and disease biology, from a surface overview it appears that TRIM E3 ubiquitin ligases are not very well recognized yet in the realm of drug discovery. This article will review some of the blockbuster scientific discoveries and technological innovations from the world of ubiquitination and E3 ubiquitin ligases that have impacted the biopharma community, from biotech colossuses to startups, and will attempt to evaluate the future of TRIM family proteins in the province of E3 ubiquitin ligase-based drug discovery.

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

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