scholarly journals Ever-Expanding NGLY1 biology

2021 ◽  
Author(s):  
Tadashi Suzuki ◽  
Yukiko Yoshida
Keyword(s):  
Genetic Disorder ◽  
Functional Characterization ◽  
Research Progress ◽  
Biological Processes ◽  
Special Issue ◽  
Core Peptide ◽  
Assay Methods ◽  
Human Genetic Disorder ◽  
Editing Enzyme

Abstract The cytosolic peptide:N-glycanase (PNGase; NGLY1 in humans) is a deglycosylating enzyme that is widely conserved in eukaryotes. This enzyme is involved in the degradation of misfolded N-glycoproteins that are destined for proteasomal degradation in the cytosol, a process that is called endoplasmic reticulum (ER)-associated degradation (ERAD). Although the physiological significance of NGLY1 remained unknown until recently, the discovery of NGLY1 deficiency, a human genetic disorder bearing mutations in the NGLY1 gene, has led to explosive research progress regarding the functional characterization of this enzyme. For example, it is now known that NGLY1 can also act as an “editing enzyme” to convert N-glycosylated asparagine residues to aspartate residues, thus introducing negative charges into a core peptide and modulating the function of the target molecule. Diverse biological processes have also been found to be affected by compromised NGLY1 activity. In this special issue, recent research progress on the functional characterization of NGLY1 and its orthologues in worm/fly/rodents, assay methods/biomarkers useful for the development of therapeutics, and the comprehensive transcriptome/proteome of NGLY1-KO cells as well as patient-derived cells are discussed.

scholarly journals Functional Requirement of Noncoding Y RNAs for Human Chromosomal DNA Replication

2006 ◽  
Vol 26 (18) ◽  
pp. 6993-7004 ◽  
Author(s):  
Christo P. Christov ◽  
Timothy J. Gardiner ◽  
Dávid Szüts ◽  
Torsten Krude
Keyword(s):  
Dna Replication ◽  
Functional Characterization ◽  
Noncoding Rnas ◽  
Biological Processes ◽  
Replication Forks ◽  
Chromosomal Dna ◽  
Free System ◽  
Specific Degradation

ABSTRACT Noncoding RNAs are recognized increasingly as important regulators of fundamental biological processes, such as gene expression and development, in eukaryotes. We report here the identification and functional characterization of the small noncoding human Y RNAs (hY RNAs) as novel factors for chromosomal DNA replication in a human cell-free system. In addition to protein fractions, hY RNAs are essential for the establishment of active chromosomal DNA replication forks in template nuclei isolated from late-G1-phase human cells. Specific degradation of hY RNAs leads to the inhibition of semiconservative DNA replication in late-G1-phase template nuclei. This inhibition is negated by resupplementation of hY RNAs. All four hY RNAs (hY1, hY3, hY4, and hY5) can functionally substitute for each other in this system. Mutagenesis of hY1 RNA showed that the binding site for Ro60 protein, which is required for Ro RNP assembly, is not essential for DNA replication. Degradation of hY1 RNA in asynchronously proliferating HeLa cells by RNA interference reduced the percentages of cells incorporating bromodeoxyuridine in vivo. These experiments implicate a functional role for hY RNAs in human chromosomal DNA replication.

scholarly journals Introduction to the Toxins Special Issue on Identification and Functional Characterization of Novel Venom Components

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 336
Author(s):  
Steven D. Aird
Keyword(s):  
20Th Century ◽  
Functional Characterization ◽  
Special Issue

Throughout most of the 20th century, the toxinological literature consisted largely of pharmacological and functional characterizations of crude venoms and venom constituents, often constituents that could not be identified unambiguously [...]

scholarly journals A Novel Combined Scientific and Artistic Approach for the Advanced Characterization of Interactomes: The Akirin/Subolesin Model

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 77 ◽  
Author(s):  
Sara Artigas-Jerónimo ◽  
Juan Pastor Comín ◽  
Margarita Villar ◽  
Marinela Contreras ◽  
Pilar Alberdi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Functional Characterization ◽  
Advanced Characterization ◽  
Research Area ◽  
Dependent Manner ◽  
Biological Processes ◽  
Visual Artists ◽  
Protective Antigens ◽  
Specific Regulation

The main objective of this study was to propose a novel methodology to approach challenges in molecular biology. Akirin/Subolesin (AKR/SUB) are vaccine protective antigens and are a model for the study of the interactome due to its conserved function in the regulation of different biological processes such as immunity and development throughout the metazoan. Herein, three visual artists and a music professor collaborated with scientists for the functional characterization of the AKR2 interactome in the regulation of the NF-κB pathway in human placenta cells. The results served as a methodological proof-of-concept to advance this research area. The results showed new perspectives on unexplored characteristics of AKR2 with functional implications. These results included protein dimerization, the physical interactions with different proteins simultaneously to regulate various biological processes defined by cell type-specific AKR–protein interactions, and how these interactions positively or negatively regulate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway in a biological context-dependent manner. These results suggested that AKR2-interacting proteins might constitute suitable secondary transcription factors for cell- and stimulus-specific regulation of NF-κB. Musical perspective supported AKR/SUB evolutionary conservation in different species and provided new mechanistic insights into the AKR2 interactome. The combined scientific and artistic perspectives resulted in a multidisciplinary approach, advancing our knowledge on AKR/SUB interactome, and provided new insights into the function of AKR2–protein interactions in the regulation of the NF-κB pathway. Additionally, herein we proposed an algorithm for quantum vaccinomics by focusing on the model proteins AKR/SUB.

scholarly journals Identification and Functional Characterization of Plant MiRNA Under Salt Stress Shed Light on Salinity Resistance Improvement Through MiRNA Manipulation in Crops

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Xu ◽  
Long Zhang ◽  
Zhengmei Yang ◽  
Yiliang Wei ◽  
Tingting Dong
Keyword(s):  
Salt Stress ◽  
Functional Characterization ◽  
Salt Resistance ◽  
Research Progress ◽  
Salt Stress Response ◽  
Plant Mirna ◽  
Important Regulator ◽  
Future Direction ◽  
Salinity Resistance

Salinity, as a major environmental stressor, limits plant growth, development, and crop yield remarkably. However, plants evolve their own defense systems in response to salt stress. Recently, microRNA (miRNA) has been broadly studied and considered to be an important regulator of the plant salt-stress response at the post-transcription level. In this review, we have summarized the recent research progress on the identification, functional characterization, and regulatory mechanism of miRNA involved in salt stress, have discussed the emerging manipulation of miRNA to improve crop salt resistance, and have provided future direction for plant miRNA study under salt stress, suggesting that the salinity resistance of crops could be improved by the manipulation of microRNA.

scholarly journals Functional characterization of RNase H1 proteins in Arabidopsis thaliana

2019 ◽  
Author(s):  
Jan Kuciński ◽  
Aleksandra Kmera ◽  
M. Jordan Rowley ◽  
Pragya Khurana ◽  
Marcin Nowotny ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Functional Characterization ◽  
Plastid Dna ◽  
Biological Processes ◽  
Base Pairs ◽  
Plastid Protein ◽  
Duplication Events ◽  
Rna:Dna Hybrids ◽  
Living Organisms

ABSTRACTRNase H1 is an endonuclease specific towards RNA:DNA hybrids. Members of this protein family are present in most living organisms and are essential for removing RNA that base pairs with DNA. It prevents detrimental effects of RNA:DNA hybrids and is involved in several biological processes. We show that Arabidopsis thaliana contains four RNase H1-like proteins originating from two gene duplication events and alternative splicing. These proteins have the canonical RNase H1 activity, which requires at least four ribonucleotides for activity. Two of those proteins are nuclear, one is localized to mitochondria and one to plastids. While the nuclear RNases H1 are dispensable, the presence of at least one organellar RNase H1 is required for embryonic development. The plastid protein RNH1C affects plastid DNA copy number and sensitivity to hydroxyurea. This indicates that three genomes present in each plant cell are served by at least one specialized RNase H1 protein.

scholarly journals Disrupting proteasomal and autophagic degradation systems of misfolded alpha-sarcoglycan protein by bortezomib and givinostat combination

2021 ◽  
Author(s):  
Lucile Hoch ◽  
Nathalie Bourg ◽  
Fanny Degrugillier ◽  
Céline Bruge ◽  
Manon Benabides ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Genetic Disorder ◽  
Genetic Diseases ◽  
Functional Characterization ◽  
Gene Encoding ◽  
Autophagic Degradation ◽  
Pathway Inhibition ◽  
Shed Light

Background and Purpose: Limb-girdle muscular dystrophy type R3 (LGMD R3) is a rare genetic disorder characterized by a progressive proximal muscle weakness and caused by mutations in the SGCA gene encoding alpha-sarcoglycan (α-SG). Here, we report the results of a mechanistic screening ascertaining the molecular mechanisms involved in the degradation of the most prevalent misfolded R77C-α-SG protein. Experimental Approach: We performed a combinatorial study to identify drugs potentializing the effect of a low dose of the proteasome inhibitor bortezomib on the R77C-α-SG degradation inhibition. Key Results: Analysis of the screening associated to artificial intelligence-based predictive ADMET characterization of the hits led to identification of the HDAC inhibitor givinostat as potential therapeutical candidate. Functional characterization revealed that givinostat effect was related to autophagic pathway inhibition, unveiling new theories concerning degradation pathways of misfolded SG proteins. Conclusion and Implications: Beyond the identification of a new therapeutic option for LGMD R3 patients, our results shed light on the potential repurposing of givinostat for the treatment of other genetic diseases sharing similar protein degradation defects such as LGMD R5 and cystic fibrosis.

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Sign in / Sign up

Export Citation Format

Share Document