Israel Journal of Chemistry最新文献

N⁶-methyladenosine (m⁶A), as the most abundant and well-studied RNA modification, can be reversibly added or removed by m⁶A methyltransferase and demethylase. The further molecular and biological function of m⁶A is achieved by the recognition of its binding protein. m⁶A functions in the diverse progress of RNA processing, including transcription regulation, splicing, nuclear export, stability, and translation, to regulate the fate of cells. Although been extensively studied in various animal cell systems, research on m⁶A's regulatory functions in plant cells lags. In recent years, with a deepening understanding of the functions of m⁶A and the development of various sequencing technologies, researches on m⁶A in plant cells have gradually increased. In this review, we focused on discussing the molecular functions of m⁶A in the nucleus and cytoplasm, aiming to elucidate the specific molecular mechanisms by which m⁶A regulates the fate of RNAs in plants. Finally, we provide some perspectives on future investigations of the detailed molecular mechanism of m⁶A-mediated regulation in plants, which might provide insights into future strategies for achieving multiple growth regulatory processes in crops.

Nucleic acid modifications play essential roles in diverse biological processes, ranging from gene expression regulation to stress response. While traditional research focused on common modifications like methylation, recent discoveries are unveiling a wide range of rare modifications with potentially crucial functions. However, accurately detecting and mapping these modifications pose significant challenges due to their low abundance and diverse chemical properties. This article summarizes the recent discoveries of rare DNA and RNA modifications across various organisms, highlighting their potential biological significance. Furthermore, it critically evaluates the limitations of current mapping techniques, including potential sources of false positives and negatives. Finally, the article discusses emerging strategies for overcoming these challenges and future opportunities in the field of rare nucleic acid modification detection.

Proteins are synthesized within ribosomes through the polymerization of amino acids (AAs). This process requires prior activation of AAs through aminoacylation that attaches them to their corresponding transfer RNAs (tRNAs). Within cells, this attachment is facilitated by aminoacyl-tRNA synthetase, resulting in a tRNA:AA conjugate. A set of ribozymes developed to acylate tRNA with non-canonical substrates enables this process outside the confines of living cells, thereby facilitating the synthesis of novel bio-based products. In modern biotechnology, aminoacylating ribozymes contribute to the production of innovative bio-based materials bearing functional non-canonical chemical substrates (NCSs) and fill the gaps in synthesizing unique polymeric backbones, extending the scope beyond traditional peptide bonds. This review summarizes current understanding of flexizymes at the molecular level and their application in generating exceptional polymeric backbones through ribosome-mediated synthesis in vitro.

Biomembranes function as hydrophobic barriers for hydrophilic substances enabling compartmentalization in biological systems. This poses, however, a problem for the targeted introduction of cargo into cells. The result is a high demand for delivery pathways into cells with the goal to investigate biological processes or to treat diseases by improved delivery. Polycationic cell-penetrating peptides (CPPs) are interesting as they can cross cell membranes and transport attached cargos directly into the cytosol. Their efficiency can be improved by anionic amphiphilic counterion activators, which bind to the CPPs to form charge-neutralized counterion-CPP complexes with sufficient hydrophobicity to cross the lipid bilayer membrane. This review summarizes recent results, which establish amphiphilic calixarenes as a new class of biocompatible and non-cytotoxic counterion activators with very high transport activities at nanomolar concentrations. We also include a brief summary of fluorescence-based assays with large unilamellar vesicles (LUVs) to investigate counterion-activated transport. Current methods use liposome-encapsulated, supramolecular host-dye reporter pairs including calixarenes, which provide new mechanistic insights and enable rapid in vitro identification of suitable activators. Taken together, amphiphilic calixarenes are currently emerging as prime candidates for counterion activation of membrane transport, which are highly modifiable and can be specifically tailored towards different cargoes and membrane types.

Herbal medicines (HMs) are gaining increasing popularity and recognition worldwide due to their eco-friendliness and efficacy. With their multi-compounds, multi-targets, and multi-pathways characteristics, HMs have been used in treatment of various diseases. However, the clinical applications of preparations containing HMs have been limited due to their inherent physicochemical properties, including low water solubility, poor stability, and unsatisfactory bioavailability of bioactive compounds. Supramolecular macrocyclic hosts, like cyclodextrins, calixarenes, cucurbiturils, and pillararenes, are important objects of researches in supramolecular chemistry. These hosts have been utilized to encapsulate the ingredients, improve the solubility of poorly water-soluble components, enhance the stability of the tested compounds, increase the bioavailability of bioactive compounds, and ensure the safety of HMs. Herein, we provide a brief introduction to the theories of supramolecular chemistry and summarize the extensive applications of supramolecular macrocyclic hosts in the field of HMs. These applications encompass the screening of bioactive compounds in HMs and the enhancement of druggability for HMs. We hope this review can provide a strategy for dealing with the challenges of HMs, thereby enabling their better applications and development.

In ribosomal synthesis of peptides and proteins, genetic information is translated into an amino acid polymer according to the genetic code, which describes the translational command encoded by each codon. However, parts of the genetic code can be adjusted to customize translations. One option is to remove decoding for a specific codon, resulting in a vacant codon. Such vacant codons can be used to stall the ribosome for mechanistic studies and display techniques. Alternatively, the liberated codon can be assigned to encode for incorporation of a noncanonical building block for expansion of the genetic code. In this review we provide an overview of the methods currently available for vacating codons in prokaryotic translation (agnostic of how these are later applied), targeting factors such as amino-acyl tRNA synthetases, tRNA, release factors, and the initiation machinery. Moreover, we assess applicability and compatibility of the currently available techniques and discuss which have the potential to develop into even more powerful approaches in the future.

A promising, but not yet practiced, approach to the treatment of neurotoxic organophosphate poisoning is the administration of a scavenger that rapidly deactivates the nerve agent before it can exert its toxic effects. The detoxification rates required for successful use of this therapy can currently only be achieved with enzymes, but synthetic scavengers, whose mode of action is based on key concepts of supramolecular chemistry, are an attractive alternative. Considerable progress has recently been made in the development of such scavengers, and compounds from several receptor classes are now available that not only bind nerve agents but also degrade them at promising rates. This review provides an overview of the field and highlights recent developments.

Our understanding of physical properties of quasicrystals owes a great deal to studies of tight-binding models constructed on quasiperiodic tilings. Among the large number of possible quasiperiodic structures, two dimensional tilings are of particular importance – in their own right, but also for information regarding properties of three dimensional systems. We provide here a users manual for those wishing to construct and study physical properties of the 8-fold Ammann–Beenker quasicrystal, a good starting point for investigations of two dimensional quasiperiodic systems. This tiling has a relatively straightforward construction. Thus, geometrical properties such as the type and number of local environments can be readily found by simple analytical computations. Transformations of sites under discrete scale changes – called inflations and deflations – are easier to establish compared to the celebrated Penrose tiling, for example. We have aimed to describe the methodology with a minimum of technicalities but in sufficient detail so as to enable non-specialists to generate quasiperiodic tilings and periodic approximants, with or without disorder. The discussion of properties includes some relations not previously published, and examples with figures.

The intricate network of cell functions relies on gene expression programs, where the whole RNA life cycle from DNA to protein is subjected to extensive transcriptional and post-transcriptional gene regulation events. Established bulk RNA sequencing methods provide an averaged, transcriptome-wide quantification of the RNA life cycle, including transcription, processing, translation, transport, and degradation through RNA-protein interactions. Furthermore, numerous studies using bulk epitranscriptomic profiling unveiled that dynamic RNA modifications (e. g., N⁶-Methyladenosine), add another layer of gene regulations. However, many regulatory events are cell-type specific, subcellularly localized, and subjected to cell-cell communications within the native tissue environment. Thanks to the advances in single-cell sequencing, spatial sequencing, and highly multiplexed imaging methods, we can routinely measure single-cell and spatial transcriptomics. Yet more comprehensive methods to profile every step of the RNA life cycle with single-cell and spatial information are still lacking. In this review, we will summarize and compare early explorations in developing state-of-the-art methods for spatially and single-cell resolved mapping of RNA kinetics, translation, RNA-protein interactions, and epitranscriptomics. It is promising that these new techniques will greatly facilitate our understanding of the RNA-centered regulation landscapes in different cell types and how the post-transcriptional regulations are interconnected within cellular and tissue architecture.

Cellular DNA and RNA are decorated with diverse chemical modifications, which add new layers to gene regulation and play crucial roles across development and disease progression. Interest in understanding the functions of DNA and RNA modifications, as well as the related molecular mechanisms, has been growing, driving progress in developing chemical and biochemical tools to detect specific modifications. New technologies are important not only for uncovering biological functions, but also for driving conceptual revolutions. In this review, we highlighted our recent advances in developing new chemical tools to detect DNA and RNA modifications in a direct, quantitative, and base-resolution manner. These includes a novel borane reduction chemistry for DNA methylation sequencing; new cytosine modificaiton oxdation chemistry for enhanced DNA hydroxymethylation sequencing; and a novel bromoacrylamide cyclization chemistry for RNA pseudouridylation sequencing. We present a mechanistic overview of these tools and their applications in epigenetic and epitranscriptomic research.