Biology subjects

Nishimoto, Y.

Publications and source records attributed to Nishimoto, Y..

4 recordsLinked to original sources

bioRxiv2025

EXOSC10-mediated pre-tRNA surveillance safeguards neuron survival

tRNA quality control pathways have been identified in yeast, whereby aberrant and hypomodified mature tRNAs are targeted for 5-3 degradation by the rapid tRNA decay (RTD) pathway involving the Xrn1 and Rat1/Xrn2 exonucleases, whereas aberrant precursor tRNAs (pre-tRNAs) are targeted for 3-5 degradation by the nuclear surveillance pathway involving the RNA Exosome. However, the pathways controlling tRNA and pre-tRNA degradation in mammals have not yet been defined and the relevance of pre-tRNA surveillance pathways for normal cell physiology remains largely unknown. The RNA Exosome comprises a core of nine non-catalytic subunits (EXOSC1-9) to which the distinct, DIS3 and EXOSC10, 3-5 exonucleases associate. Here we find that EXOSC10 deficiency leads to accumulation of unspliced precursor tRNAs (pre-tRNAs) in mouse embryonic stem cells (ESCs) and is required for pre-tRNA decay in biochemical assays. Pre-tRNA overexpression causes diminished motor neuronal survival in a mouse ESC differentiation model. Our results identify a pre-tRNA decay pathway that links Exosome deficiency with neuron survival and provides insight into possible pathological mechanisms underlying human neurodevelopmental disorders caused by mutations in Exosome subunits and genes involved in tRNA biogenesis. O_LIExosc10 is required for pre-tRNA surveillance in cells and degradation in biochemical assays C_LIO_LIPre-tRNA expression inhibits survival of neurons C_LIO_LIPre-tRNA decay pathway links exosome deficiency with neurodevelopmental disorders C_LI

molecular biology↗

bioRxiv2025

Hexanoic acid improves metabolic health in mice fed high-fat diet.

BackgroundOverweight and obesity is currently a worldwide problem with undesirable health consequences such as type 2 diabetes. Therefore, much attention has been paid to preventing obesity through diet. Free fatty acids (FFAs) are an important energy source, and they also serve as signaling molecules in many biological processes leading to an increased energy expenditure and insulin secretion. Short-chain fatty acids (SCFAs) such as acetic, propionic and butyric acid are the bioactive metabolites produced by gut microbes, and their beneficial effects on host metabolism are well-studied. In addition, medium-chain fatty acids (MCFAs) such as octanoic and decanoic acid also play a positive role in regulating lipid and glucose metabolisms. However, the effects of hexanoic acid on metabolism are poorly understood. Therefore, this study investigated the role of hexanoic acid on lipid and glucose metabolism in mice. MethodsMale C57BL/6J mice were fed normal chow diet, high-fat diet (HFD), HFD-containing 5% butyric acid or HFD-containing 5% hexanoic acid for 4 weeks, and the effects of hexanoic acid on lipid and glucose metabolism were examined. ResultsButyric acid and hexanoic acid prevented body weight gain and fat accumulation in white adipose tissues under HFD-feeding. In addition, both FFAs suppressed the elevated plasma levels of non-esterified fatty acid (NEFA) and hepatic triglyceride content induced by HFD. The expression levels of genes involved in fatty acid biosynthesis were decreased in white adipose tissues by oral supplementation of butyric acid or hexanoic acid. Mice fed HFD also exhibited hyperglycemia and hyperinsulinemia, and these impaired glucose metabolisms improved by hexanoic acid. Hexanoic acid increased the expression levels of genes associated with gluconeogenesis, and improved insulin sensitivity in mice fed HFD. ConclusionsThis study highlights the importance of hexanoic acid in improvement of lipid and glucose metabolisms. Thus, our findings provide insight into the development of functional foods which prevent obesity-related disease such as type 2 diabetes.

physiology↗

bioRxiv2023

The role of desmoplakin for neuronal function in the dentate gyrus and anxiety-related behavior

Desmoplakin (Dsp) is a component of desmosomal cell-cell junctions that interacts with the cadherin complex and cytoskeletal intermediate filaments. In addition to its function as an adhesion component, Dsp is involved in various biological processes, such as gene expression, differentiation, and migration. Dsp is specifically expressed in the hippocampal dentate gyrus (DG) in the central nervous system. However, it is unclear how Dsp impacts hippocampal function and its related behaviors. Using an adeno-associated virus knockdown system in mice, we provide evidence that Dsp in the DG maintains hippocampal functions, including neuronal activity and adult neurogenesis, and contributes to anxiolytic-like effects. Dsp protein is mostly localized in mature granule cells in the adult DG. Dsp knockdown in the DG resulted in a lowered expression of an activity-dependent transcription factor FosB, and an increased expression of mature neuronal markers, such as calbindin. In addition, the suppression of Dsp decreases serotonin responsiveness at the DG output mossy fiber synapses and alters adult neurogenic processes in the subgranular zone of the DG. Moreover, DG- specific Dsp knockdown mice showed an increase in anxiety-like behaviors. Taken together, this research uncovers an unexplored function for Dsp in the central nervous system and suggests that Dsp in the DG may function as a regulator to maintain proper neuronal activation and adult neurogenesis, and contribute to the adaptation of emotion-related behavior.

neuroscience↗

bioRxiv2020

Conservation and host-specific expression of non-tandemly repeated heterogenous ribosome RNA gene in arbuscular mycorrhizal fungi

The ribosomal RNA-encoding gene (rDNA) has a characteristic genomic nature: tens to thousands of copies in a genome, tandemly repeated structure, and intragenomic sequence homogeneity. These features contribute to ribosome productivity via physiological and evolutionary processes. We reported previously the exceptional absence of these features in the model arbuscular mycorrhizal (AM) fungus Rhizophagus irregularis. Here we examine the phylogenetic distribution of the exceptional rDNA features in the genus Rhizophagus via improving the genome sequence of R. clarus. Cross-species comparison indicated similarity of their rDNAs not only in the genomic features but also in the distribution of intragenomic polymorphic sites on the paralogs. Ribosomal RNA comprises multiple domains with different functions. The two Rhizophagus species commonly exhibited a variation enrichment site, ES27L, which is related to translational fidelity and antibiotic sensitivity. Variation enrichment on ES27L has not been observed in other organisms lacking the three rDNA features such as malaria parasites and Cyanidioschyzon merolae. Expression profiling of rDNAs in R. irregularis revealed that rDNA paralogs are expressed differently in association with host plant species. Our results suggest a broad distribution of the disarranged rDNA across AM fungi and its involvement in the successful association with the broad range of host species.

genomics↗