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Nature Reviews. Molecular Cell Biology Nov 2017Precursor messenger RNA (pre-mRNA) splicing is an essential step in the flow of information from DNA to protein in all eukaryotes. Research over the past four decades... (Review)
Review
Precursor messenger RNA (pre-mRNA) splicing is an essential step in the flow of information from DNA to protein in all eukaryotes. Research over the past four decades has molecularly delineated the splicing pathway, including characterization of the detailed splicing reaction, definition of the spliceosome and identification of its components, and biochemical analysis of the various splicing complexes and their regulation. Structural information is central to mechanistic understanding of pre-mRNA splicing by the spliceosome. X-ray crystallography of the spliceosomal components and subcomplexes is complemented by electron microscopy of the intact spliceosome. In this Review, I discuss recent atomic-resolution structures of the intact spliceosome at different stages of the splicing cycle. These structures have provided considerable mechanistic insight into pre-mRNA splicing and have corroborated and explained a large body of genetic and biochemical data. Together, the structural data have proved that the spliceosome is a protein-directed metalloribozyme.
Topics: Animals; Crystallography, X-Ray; Humans; Microscopy, Electron; RNA Precursors; RNA Splicing; RNA, Catalytic; Spliceosomes; Structure-Activity Relationship
PubMed: 28951565
DOI: 10.1038/nrm.2017.86 -
Materials Horizons Apr 2023With the rapid development of integrated electronics and optoelectronics, methods for the scalable industrial-scale growth of two-dimensional (2D) transition metal... (Review)
Review
With the rapid development of integrated electronics and optoelectronics, methods for the scalable industrial-scale growth of two-dimensional (2D) transition metal dichalcogenide (TMD) materials have become a hot research topic. However, the control of gas distribution of solid precursors in common chemical vapor deposition (CVD) is still a challenge, resulting in the growth of 2D TMDs strongly influenced by the location of the substrate from the precursor powder. In contrast, liquid-precursor-intermediated growth not only avoids the use of solid powders but also enables the uniform distribution of precursors on the substrate through spin-coating, which is much more favorable for the synthesis of wafer-scale TMDs. Moreover, the spin-coating process based on liquid precursors can control the thickness of the spin-coated films by regulating the solution concentration and spin-coating speed. Herein, this review focuses on the recent progress in the synthesis of 2D TMDs based on liquid-precursor-intermediated CVD (LPI-CVD) growth. Firstly, the different assisted treatments based on LPI-CVD strategies for monolayer 2D TMDs are introduced. Then, the progress in the regulation of the different physical properties of monolayer 2D TMDs by substitution of the transition metal and their corresponding heterostructures based on LPI-CVD growth are summarized. Finally, the challenges and perspectives of 2D TMDs based on the LPI-CVD method are discussed.
PubMed: 36628937
DOI: 10.1039/d2mh01207c -
International Journal of Molecular... Dec 2021With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow... (Review)
Review
With few exceptions, proteins that constitute the proteome of mitochondria originate outside of this organelle in precursor forms. Such protein precursors follow dedicated transportation paths to reach specific parts of mitochondria, where they complete their maturation and perform their functions. Mitochondrial precursor targeting and import pathways are essential to maintain proper mitochondrial function and cell survival, thus are tightly controlled at each stage. Mechanisms that sustain protein homeostasis of the cytosol play a vital role in the quality control of proteins targeted to the organelle. Starting from their synthesis, precursors are constantly chaperoned and guided to reduce the risk of premature folding, erroneous interactions, or protein damage. The ubiquitin-proteasome system provides proteolytic control that is not restricted to defective proteins but also regulates the supply of precursors to the organelle. Recent discoveries provide evidence that stress caused by the mislocalization of mitochondrial proteins may contribute to disease development. Precursors are not only subject to regulation but also modulate cytosolic machinery. Here we provide an overview of the cellular pathways that are involved in precursor maintenance and guidance at the early cytosolic stages of mitochondrial biogenesis. Moreover, we follow the circumstances in which mitochondrial protein import deregulation disturbs the cellular balance, carefully looking for rescue paths that can restore proteostasis.
Topics: Cell Survival; Cytosol; Humans; Mitochondria; Mitochondrial Proteins; Organelle Biogenesis; Protein Precursors; Protein Transport
PubMed: 35008433
DOI: 10.3390/ijms23010007 -
Foods (Basel, Switzerland) Jul 2022Volatile polyfunctional thiol compounds, particularly 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHA), are key odorants contributing to the aroma profile... (Review)
Review
Volatile polyfunctional thiol compounds, particularly 3-sulfanylhexan-1-ol (3SH) and 3-sulfanylhexyl acetate (3SHA), are key odorants contributing to the aroma profile of many wine styles, generally imparting tropical grapefruit and passionfruit aromas. 3SH and 3SHA are present in negligible concentrations in the grape berry, juice, and must, suggesting that they are released from non-volatile precursors present in the grape. The exploration of the nature and biogenesis of these precursors to 3SH and 3SHA has proven important for the elucidation of polyfunctional thiol biogenesis during alcoholic fermentation. The development and validation of appropriate analytical techniques for the analysis of 3SH precursors in enological matrices have been extensive, and this review explores the analysis and discovery of these precursor compounds. The development of analytical methods to analyze 3SH precursors, from the selection of the analytical instrument, sample preparation, and methods for standardization, will first be discussed, before highlighting how these techniques have been used in the elucidation of the biogenesis of 3SH and 3SHA in grape wines. Lastly, the future of thiol precursor analysis will be considered, with the development of new methods that greatly reduce the sample preparation time and enable multiple precursors, and the thiols themselves, to be quantitated using a single method.
PubMed: 35885295
DOI: 10.3390/foods11142050 -
Biomolecular Concepts Mar 2015Beta-amyloid precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. APP plays a central role... (Review)
Review
Beta-amyloid precursor protein (APP) is a membrane-spanning protein with a large extracellular domain and a much smaller intracellular domain. APP plays a central role in Alzheimer's disease (AD) pathogenesis: APP processing generates β-amyloid (Aβ) peptides, which are deposited as amyloid plaques in the brains of AD individuals; point mutations and duplications of APP are causal for a subset of early-onset familial AD (FAD) (onset age <65 years old). However, these mutations in FAD represent a very small percentage of cases (∼1%). Approximately 99% of AD cases are nonfamilial and late-onset, i.e., sporadic AD (SAD) (onset age >65 years old), and the pathophysiology of this disorder is not yet fully understood. APP is an extremely complex molecule that may be functionally important in its full-length configuration, as well as the source of numerous fragments with varying effects on neural function, yet the normal function of APP remains largely unknown. This article provides an overview of our current understanding of APP, including its structure, expression patterns, proteolytic processing and putative functions. Importantly, and for the first time, my recent data concerning its epigenetic regulation, especially in alternative APP pre-mRNA splicing and in the control of genomic rearrangements of the APP gene, are also reported. These findings may provide new directions for investigating the role of APP in neuropathology associated with a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt) found in patients with Lesch-Nyhan syndrome (LNS) and its attenuated variants (LNVs). Also, these findings may be of significance for research in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome (FXS) and AD, with its diversity and complexity, SAD in particular. Accurate quantification of various APP-mRNA isoforms in brain tissues is needed, and antisense drugs are potential treatments.
Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Epigenesis, Genetic; Humans; Neurodegenerative Diseases; Neurodevelopmental Disorders; RNA Precursors; RNA Splicing
PubMed: 25719338
DOI: 10.1515/bmc-2014-0041 -
Frontiers in Microbiology 2019Microbial secondary metabolites (MSMs) have played and continue to play a highly significant role in the drug discovery and development process. Genetically, MSM... (Review)
Review
Microbial secondary metabolites (MSMs) have played and continue to play a highly significant role in the drug discovery and development process. Genetically, MSM chemical structures are biologically synthesized by microbial gene clusters. Recently, however, the speed of new bioactive MSM discovery has been slowing down due to consistent employment of conventional cultivation and isolation procedure. In order to alleviate this challenge, a number of new approaches have been developed. The strategy of one strain many compounds (OSMAC) has been shown as a simple and powerful tool that can activate many silent biogenetic gene clusters in microorganisms to make more natural products. This review highlights important and successful examples using OSMAC approaches, which covers changing medium composition and cultivation status, co-cultivation with other strain(s), adding enzyme inhibitor(s) and MSM biosynthetic precursor(s). Available evidences had shown that variation of cultivation condition is the most effective way to produce more MSMs and facilitate the discovery of new therapeutic agents.
PubMed: 30863377
DOI: 10.3389/fmicb.2019.00294 -
Nature Protocols Aug 2021Many supramolecular materials in biological systems are driven to a nonequilibrium state by the irreversible consumption of high-energy molecules such as ATP or GTP. As... (Review)
Review
Many supramolecular materials in biological systems are driven to a nonequilibrium state by the irreversible consumption of high-energy molecules such as ATP or GTP. As a result, they exhibit unique dynamic properties such as a tunable lifetime, adaptivity or the ability to self-heal. In contrast, synthetic counterparts that exist in or close to equilibrium are controlled by thermodynamic parameters and therefore lack these dynamic properties. To mimic biological materials more closely, synthetic self-assembling systems have been developed that are driven out of equilibrium by chemical reactions. This protocol describes the synthesis and characterization of such an assembly, which is driven by carbodiimide fuels. Depending on the amount of chemical fuel added to the material, its lifetime can be tuned. In the first step, the protocol details the synthesis and purification of the peptide-based precursors for the fuel-driven assemblies by solid-phase peptide synthesis. Then, we explain how to analyze the kinetic response of the precursors to a carbodiimide-based chemical fuel by HPLC and kinetic models. Finally, we detail how to study the emerging assembly's macro- and microscopic properties by time-lapse photography, UV-visible spectroscopy, shear rheology, confocal laser scanning microscopy and electron microscopy. The procedure is described using the example of a colloid-forming precursor Fmoc-E-OH and a fiber-forming precursor Fmoc-AAD-OH to emphasize the differences in characterization depending on the type of assembly. The characterization of a precursor's transient assembly can be done within 5 d. The synthesis and purification of a peptide precursor requires 2 d of work.
Topics: Carbodiimides; Cryoelectron Microscopy; Humans; Macromolecular Substances; Microscopy, Confocal; Microscopy, Electron, Transmission; Models, Molecular; Molecular Structure
PubMed: 34194049
DOI: 10.1038/s41596-021-00563-9 -
Recent Patents on Nanotechnology 2016Recent advances in nanotechnology make novel shapes of nanostructured materials with novel physicochemical properties. Different kinds of materials including carbon,... (Review)
Review
BACKGROUND
Recent advances in nanotechnology make novel shapes of nanostructured materials with novel physicochemical properties. Different kinds of materials including carbon, metals, alloys, metal oxides, conducting polymers, metal chalcogenides, pnictides and fluorides have been synthesized with small size of <100 nm with shapes resembled to the natural flowers. The objective of this review is to provide a broad overview of the synthesis strategies, effects of different parameters on the morphology of nanoflowers, and their applications.
METHODS
A comprehensive search to assess the current evidence for the synthesis routs of nanoflowers and applications was conducted. 487 studies became selected and the quality of papers were appraised and categorized according to type of nanomaterials. Within each section, the nanomaterials addressed specifically. In addition, recent patents were reviewed in a separate section.
RESULTS
The nanoflowers exhibited unique properties which were utilized in the design of efficient applications. These nanostructures can be processed with different methods. The configuration of flower-like nanostructures can be controlled by altering experimental parameters, such as the precursor`s ratio, temperature and reaction time. Despite the huge efforts to control and understand the growth mechanism of these nanostructures, some fundamental phenomena are still not well understood. Investigation of the fundamental effects of size and morphology on their properties is required in order to better apply these nanostructured materials.
CONCLUSION
The nanoflowers with interesting properties can be used in the design of future devices with various applications. The existence of different routes to synthesis nanoflowers and their unique properties confirm the importance promoted awareness of potential benefits of nanoflowers in different applications. The reviewed patents emphasized the importance of these nanostructures. Therefore, research efforts based on nanoflowers are dynamic and applicable in various fields.
PubMed: 27502388
DOI: 10.2174/1872210510999160517102102 -
European Archives of Psychiatry and... Apr 2016
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Humans; Protein Precursors; Rats; Serotonin
PubMed: 26899501
DOI: 10.1007/s00406-016-0682-9 -
Cellulose (London, England) 2021Polyacrylonitrile (PAN)-based carbon precursor is a well-established and researched material for electrodes in energy storage applications due to its good physical... (Review)
Review
Polyacrylonitrile (PAN)-based carbon precursor is a well-established and researched material for electrodes in energy storage applications due to its good physical properties and excellent electrochemical performance. However, in the fight of preserving the environment and pioneering renewable energy sources, environmentally sustainable carbon precursors with superior electrochemical performance are needed. Therefore, bio-based materials are excellent candidates to replace PAN as a carbon precursor. Depending on the design requirement (e.g. carbon morphology, doping level, specific surface area, pore size and volume, and electrochemical performance), the appropriate selection of carbon precursors can be made from a variety of biomass and biowaste materials. This review provides a summary and discussion on the preparation and characterization of the emerging and recent bio-based carbon precursors that can be used as electrodes in energy storage applications. The review is outlined based on the morphology of nanostructures and the precursor's type. Furthermore, the review discusses and summarizes the excellent electrochemical performance of these recent carbon precursors in storage energy applications. Finally, a summary and outlook are also given. All this together portrays the promising role of bio-based carbon electrodes in energy storage applications.
PubMed: 33897123
DOI: 10.1007/s10570-021-03881-z