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Scientific Reports Aug 2023RNA-binding protein Musashi1 (MSI1) shows an increased expression level in several cancers and has been introduced as a prognostic marker in some malignancies. It is...
RNA-binding protein Musashi1 (MSI1) shows an increased expression level in several cancers and has been introduced as a prognostic marker in some malignancies. It is expected that if any miRNA is encoded by this gene, it might have a role in cancer development or could be considered as a prognostic biomarker. Accordingly, in this study, we aimed to find novel miRNA(s) inside the intronic regions of the MSI1 gene. Here, we report two novel miRNAs within intron 4 of MSI1 gene, named MSM2 and MSM3, which were selected among several miRNA precursors predicted by bioinformatic studies. For experimental analysis, corresponding precursor miRNAs were transfected into HEK293T cells and exogenous expression of the mature miRNAs were detected. Two mature miRNAs, MSM3-3p and MSM3-5p were generated by MSM3 precursor and one, MSM2-5p was derived from MSM2. Besides, endogenous expression of MSM2-5p and MSM3-3p was detected in MCF-7 and SH-SY5Y cell lines. Expression of both mature miRNAs was also detected in clinical samples of breast cancer. Additionally, the interaction between the MSM3-3p and 3'UTR region of PDE11A was confirmed by dual luciferase assay. Overall, our data demonstrated that MSI1 gene encodes two novel miRNAs in breast cancer cells.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; HEK293 Cells; Neuroblastoma; Oncogenes; Nerve Tissue Proteins; RNA-Binding Proteins
PubMed: 37607966
DOI: 10.1038/s41598-023-40666-9 -
Biological Chemistry Oct 2023The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I... (Review)
Review
The ribosomal RNA precursor (pre-rRNA) comprises three of the four ribosomal RNAs and is synthesized by RNA polymerase (Pol) I. Here, we describe the mechanisms of Pol I transcription in human cells with a focus on recent insights gained from structure-function analyses. The comparison of Pol I-specific structural and functional features with those of other Pols and with the excessively studied yeast system distinguishes organism-specific from general traits. We explain the organization of the genomic rDNA loci in human cells, describe the Pol I transcription cycle regarding structural changes in the enzyme and the roles of human Pol I subunits, and depict human rDNA transcription factors and their function on a mechanistic level. We disentangle information gained by direct investigation from what had apparently been deduced from studies of the yeast enzymes. Finally, we provide information about how Pol I mutations may contribute to developmental diseases, and why Pol I is a target for new cancer treatment strategies, since increased rRNA synthesis was correlated with rapidly expanding cell populations.
Topics: Humans; RNA, Ribosomal; RNA Precursors; Saccharomyces cerevisiae; Transcription, Genetic; RNA Polymerase I; DNA, Ribosomal
PubMed: 37454246
DOI: 10.1515/hsz-2023-0214 -
Biotechnology Advances Oct 2023Glycosylation is how proteins and lipids are modified with complex carbohydrates known as glycans. The post-translational modification of proteins with glycans is not a... (Review)
Review
Glycosylation is how proteins and lipids are modified with complex carbohydrates known as glycans. The post-translational modification of proteins with glycans is not a template-driven process in the same way as genetic transcription or protein translation. Glycosylation is instead dynamically regulated by metabolic flux. This metabolic flux is determined by the concentrations and activities of the glycotransferase enzymes, which synthesise glycans, the metabolites that act as their precursors and transporter proteins. This review provides an overview of the metabolic pathways underlying glycan synthesis. Pathological dysregulation of glycosylation, particularly increased glycosylation occurring during inflammation, is also elucidated. The resulting inflammatory hyperglycosylation acts as a glycosignature of disease, and we report on the changes in the metabolic pathways which feed into glycan synthesis, revealing alterations to key enzymes. Finally, we examine studies in developing metabolic inhibitors targeting these critical enzymes. These results provide the tools for researchers investigating the role of glycan metabolism in inflammation and have helped to identify promising glycotherapeutic approaches to inflammation.
Topics: Glycosylation; Polysaccharides; Metabolic Networks and Pathways
PubMed: 37290585
DOI: 10.1016/j.biotechadv.2023.108184 -
Molecular Biology of the Cell Sep 2023Almost all mitochondrial proteins are synthesized in the cytosol and subsequently targeted to mitochondria. The accumulation of nonimported precursor proteins occurring...
Almost all mitochondrial proteins are synthesized in the cytosol and subsequently targeted to mitochondria. The accumulation of nonimported precursor proteins occurring upon mitochondrial dysfunction can challenge cellular protein homeostasis. Here we show that blocking protein translocation into mitochondria results in the accumulation of mitochondrial membrane proteins at the endoplasmic reticulum, thereby triggering the unfolded protein response (UPR). Moreover, we find that mitochondrial membrane proteins are also routed to the ER under physiological conditions. The level of ER-resident mitochondrial precursors is enhanced by import defects as well as metabolic stimuli that increase the expression of mitochondrial proteins. Under such conditions, the UPR is crucial to maintain protein homeostasis and cellular fitness. We propose the ER serves as a physiological buffer zone for those mitochondrial precursors that cannot be immediately imported into mitochondria while engaging the UPR to adjust the ER proteostasis capacity to the extent of precursor accumulation.
Topics: Endoplasmic Reticulum Stress; Organelle Biogenesis; Unfolded Protein Response; Endoplasmic Reticulum; Mitochondrial Proteins
PubMed: 37379206
DOI: 10.1091/mbc.E23-05-0205 -
Critical Reviews in Food Science and... Jul 2023Natural animal-based flavors have great appeal to consumers and have broad applications in the food industry. In this review, we summarized findings related to bacon and... (Review)
Review
Natural animal-based flavors have great appeal to consumers and have broad applications in the food industry. In this review, we summarized findings related to bacon and Cheddar cheese flavors' components and their precursors, reaction mechanisms, influential factors, and characterization methods. The results show that free sugars, free amino acids, peptides, vitamins, lipids, and nitrites are precursors to bacon flavor. The conditions governing the formation of bacon flavor are thermally dependent, which facilitates the use of thermal food processing to generate such a flavor. For Cheddar cheese flavor, milk ingredients such as lactose, citrate, fat, and casein are reported as precursors. The optimum conditions to generate Cheddar cheese flavor from precursors are quite strict, which limits its application in food processing. As an alternative, it is more practical to generate Cheddar cheese flavor by combining key aroma compounds using thermal food processing. This review provides the food industry the comprehensive information about the generation of bacon and Cheddar cheese flavors using precursor molecules.
PubMed: 37431669
DOI: 10.1080/10408398.2023.2230497 -
ChemPlusChem Jun 2024A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with radiochemical conversions (RCCs) of up to 90%. Both electron rich and...
A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with radiochemical conversions (RCCs) of up to 90%. Both electron rich and electron poor substrates were successfully radiolabeled at room temperature (RT) using relatively low precursor amounts (0.15 µmol/ 0.02 mL solvent (7.5 mM)). Ready access to ortho-, para- and meta- astatinated arenes was achievable. Optimized reaction conditions were successfully applied to label a poly (ADP-ribose) polymerase (PARP) inhibitor with a RCC of approx. 50%. We believe that trimethylgermanyl derivatives are a viable addition to the astatination precursor toolbox and facilitate astatination of arenes. The developed labeling method should easily be applicable for productions under good manufacturing practice (GMP).
PubMed: 38877386
DOI: 10.1002/cplu.202400254 -
Chemical Record (New York, N.Y.) Aug 2023Carbon materials (CMs) hold immense potential for applications across a wide range of fields. However, current precursors often confront limitations such as low... (Review)
Review
Carbon materials (CMs) hold immense potential for applications across a wide range of fields. However, current precursors often confront limitations such as low heteroatom content, poor solubility, or complicated preparation and post-treatment procedures. Our research has unveiled that protic ionic liquids and salts (PILs/PSs), generated from the neutralization of organic bases with protonic acids, can function as economical and versatile small-molecule carbon precursors. The resultant CMs display attractive features, including elevated carbon yield, heightened nitrogen content, improved graphitic structure, robust thermal stability against oxidation, and superior conductivity, even surpassing that of graphite. These properties can be elaborate modulated by varying the molecular structure of PILs/PSs. In this Personal Account, we summarize recent developments in PILs/PSs-derived CMs, with a particular focus on the correlations between precursor structure and the physicochemical properties of CMs. We aim to impart insights into the foreseeable controlled synthesis of advanced CMs.
PubMed: 37098871
DOI: 10.1002/tcr.202300064 -
BioRxiv : the Preprint Server For... Aug 2023Many bacterial surface glycans such as the peptidoglycan (PG) cell wall, O-antigens, and capsules are built from monomeric units linked to a polyprenyl lipid carrier....
Many bacterial surface glycans such as the peptidoglycan (PG) cell wall, O-antigens, and capsules are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting lipid carrier is effectively distributed among competing pathways has remained unclear for some time. Here, we describe the isolation and characterization of hyperactive variants of MraY, the essential and conserved enzyme catalyzing the formation of the first lipid-linked PG precursor called lipid I. These variants result in the elevated production of the final PG precursor lipid II in cells and are hyperactive in a purified system. Amino acid substitutions within the activated MraY variants unexpectedly map to a cavity on the extracellular side of the dimer interface, far from the active site. Our structural evidence and molecular dynamics simulations suggest that the cavity is a binding site for lipid II molecules that have been transported to the outer leaflet of the membrane. Overall, our results support a model in which excess externalized lipid II allosterically inhibits MraY, providing a feedback mechanism to prevent the sequestration of lipid carrier in the PG biogenesis pathway. MraY belongs to the broadly distributed polyprenyl-phosphate N-acetylhexosamine 1-phosphate transferase (PNPT) superfamily of enzymes. We therefore propose that similar feedback mechanisms may be widely employed to coordinate precursor supply with demand by polymerases, thereby optimizing the partitioning of lipid carriers between competing glycan biogenesis pathways.
PubMed: 37577621
DOI: 10.1101/2023.08.01.551478 -
Sensors (Basel, Switzerland) Oct 2023The characteristics of acoustic emission signals generated in the process of rock deformation and fission contain rich information on internal rock damage. The use of...
The characteristics of acoustic emission signals generated in the process of rock deformation and fission contain rich information on internal rock damage. The use of acoustic emissions monitoring technology can analyze and identify the precursor information of rock failure. At present, in the field of acoustic emissions monitoring and the early warning of rock fracture disasters, there is no real-time identification method for a disaster precursor characteristic signal. It is easy to lose information by analyzing the characteristic parameters of traditional acoustic emissions to find signals that serve as precursors to disasters, and analysis has mostly been based on post-analysis, which leads to poor real-time recognition of disaster precursor characteristics and low application levels in the engineering field. Based on this, this paper regards the acoustic emissions signal of rock fracture as a kind of speech signal generated by rock fracture uses this idea of speech recognition for reference alongside spectral analysis (STFT) and Mel frequency analysis to realize the feature extraction of acoustic emissions from rock fracture. In deep learning, based on the VGG16 convolutional neural network and AlexNet convolutional neural network, six intelligent real-time recognition models of rock fracture and key acoustic emission signals were constructed, and the network structure and loss function of traditional VGG16 were optimized. The experimental results show that these six deep-learning models can achieve the real-time intelligent recognition of key signals, and Mel, combined with the improved VGG16, achieved the best performance with 87.68% accuracy and 81.05% recall. Then, by comparing multiple groups of signal recognition models, Mel+VGG-FL proposed in this paper was verified as having a high recognition accuracy and certain recognition efficiency, performing the intelligent real-time recognition of key acoustic emission signals in the process of rock fracture more accurately, which can provide new ideas and methods for related research and the real-time intelligent recognition of rock fracture precursor characteristics.
PubMed: 37896608
DOI: 10.3390/s23208513 -
Nucleic Acids Research Oct 2023RNase P is the endonuclease responsible for the 5' processing of precursor tRNAs (pre-tRNAs). Unlike the single-subunit protein-only RNase P (PRORP) found in plants or...
RNase P is the endonuclease responsible for the 5' processing of precursor tRNAs (pre-tRNAs). Unlike the single-subunit protein-only RNase P (PRORP) found in plants or protists, human mitochondrial RNase P is a multi-enzyme assembly that in addition to the homologous PRORP subunit comprises a methyltransferase (TRMT10C) and a dehydrogenase (SDR5C1) subunit; these proteins, but not their enzymatic activities, are required for efficient pre-tRNA cleavage. Here we report a kinetic analysis of the cleavage reaction by human PRORP and its interplay with TRMT10C-SDR5C1 including 12 different mitochondrial pre-tRNAs. Surprisingly, we found that PRORP alone binds pre-tRNAs with nanomolar affinity and can even cleave some of them at reduced efficiency without the other subunits. Thus, the ancient binding mode, involving the tRNA elbow and PRORP's PPR domain, appears basically retained by human PRORP, and its metallonuclease domain is in principle correctly folded and functional. Our findings support a model according to which the main function of TRMT10C-SDR5C1 is to direct PRORP's nuclease domain to the cleavage site, thereby increasing the rate and accuracy of cleavage. This functional dependence of human PRORP on an extra tRNA-binding protein complex likely reflects an evolutionary adaptation to the erosion of canonical structural features in mitochondrial tRNAs.
Topics: Humans; Ribonuclease P; Kinetics; RNA, Transfer; RNA Precursors; Endonucleases
PubMed: 37779095
DOI: 10.1093/nar/gkad713