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Advanced Science (Weinheim,... Sep 2023Ketone bodies have long been known as a group of lipid-derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying...
Ketone bodies have long been known as a group of lipid-derived alternative energy sources during glucose shortages. Nevertheless, the molecular mechanisms underlying their non-metabolic functions remain largely elusive. This study identified acetoacetate as the precursor for lysine acetoacetylation (Kacac), a previously uncharacterized and evolutionarily conserved histone post-translational modification. This protein modification is comprehensively validated using chemical and biochemical approaches, including HPLC co-elution and MS/MS analysis using synthetic peptides, Western blot, and isotopic labeling. Histone Kacac can be dynamically regulated by acetoacetate concentration, possibly via acetoacetyl-CoA. Biochemical studies show that HBO1, traditionally known as an acetyltransferase, can also serve as an acetoacetyltransferase. In addition, 33 Kacac sites are identified on mammalian histones, depicting the landscape of histone Kacac marks across species and organs. In summary, this study thus discovers a physiologically relevant and enzymatically regulated histone mark that sheds light on the non-metabolic functions of ketone bodies.
Topics: Animals; Histones; Lysine; Acetoacetates; Tandem Mass Spectrometry; Protein Processing, Post-Translational; Mammals
PubMed: 37382194
DOI: 10.1002/advs.202300032 -
The Plant Cell Sep 2023Flowering is the transition from vegetative to reproductive growth and is critical for plant adaptation and reproduction. FLOWERING LOCUS C (FLC) plays a central role in...
Flowering is the transition from vegetative to reproductive growth and is critical for plant adaptation and reproduction. FLOWERING LOCUS C (FLC) plays a central role in flowering time control, and dissecting its regulation mechanism provides essential information for crop improvement. Here, we report that DECAPPING5 (DCP5), a component of processing bodies (P-bodies), regulates FLC transcription and flowering time in Arabidopsis (Arabidopsis thaliana). DCP5 and its interacting partner SISTER OF FCA (SSF) undergo liquid-liquid phase separation (LLPS) that is mediated by their prion-like domains (PrDs). Enhancing or attenuating the LLPS of both proteins using transgenic methods greatly affects their ability to regulate FLC and flowering time. DCP5 regulates FLC transcription by modulating RNA polymerase II enrichment at the FLC locus. DCP5 requires SSF for FLC regulation, and loss of SSF or its PrD disrupts DCP5 function. Our results reveal that DCP5 interacts with SSF, and the nuclear DCP5-SSF complex regulates FLC expression at the transcriptional level.
Topics: Arabidopsis; Arabidopsis Proteins; Co-Repressor Proteins; Flowers; Gene Expression Regulation, Plant; MADS Domain Proteins; Mutation; Processing Bodies; Reproduction
PubMed: 37220754
DOI: 10.1093/plcell/koad151 -
Seminars in Cell & Developmental Biology Apr 2024P-bodies are cytoplasmic condensates that accumulate low-translation mRNAs for temporary storage before translation or degradation. P-bodies have been best characterized... (Review)
Review
P-bodies are cytoplasmic condensates that accumulate low-translation mRNAs for temporary storage before translation or degradation. P-bodies have been best characterized in yeast and mammalian tissue culture cells. We describe here related condensates in the germline of animal models. Germline P-bodies have been reported at all stages of germline development from primordial germ cells to gametes. The activity of the universal germ cell fate regulator, Nanos, is linked to the mRNA decay function of P-bodies, and spatially-regulated condensation of P-body like condensates in embryos is required to localize mRNA regulators to primordial germ cells. In most cases, however, it is not known whether P-bodies represent functional compartments or non-functional condensation by-products that arise when ribonucleoprotein complexes saturate the cytoplasm. We speculate that the ubiquity of P-body-like condensates in germ cells reflects the strong reliance of the germline on cytoplasmic, rather than nuclear, mechanisms of gene regulation.
Topics: Animals; RNA-Binding Proteins; Processing Bodies; Germ Cells; RNA, Messenger; Gene Expression Regulation; Mammals
PubMed: 37407370
DOI: 10.1016/j.semcdb.2023.06.010 -
Molecular Cell Dec 2023In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here,...
In the cytoplasm, mRNAs are dynamically partitioned into translating and non-translating pools, but the mechanism for this regulation has largely remained elusive. Here, we report that mA regulates mRNA partitioning between polysome and P-body where a pool of non-translating mRNAs resides. By quantifying the mA level of polysomal and cytoplasmic mRNAs with mA-LAIC-seq and mA-LC-MS/MS in HeLa cells, we observed that polysome-associated mRNAs are hypo-mA-methylated, whereas those enriched in P-body are hyper-mA-methylated. Downregulation of the mA writer METTL14 enhances translation by switching originally hyper-mA-modified mRNAs from P-body to polysome. Conversely, by proteomic analysis, we identify a specific mA reader IGF2BP3 enriched in P-body, and via knockdown and molecular tethering assays, we demonstrate that IGF2BP3 is both necessary and sufficient to switch target mRNAs from polysome to P-body. These findings suggest a model for the dynamic regulation of mRNA partitioning between the translating and non-translating pools in an mA-dependent manner.
Topics: Humans; Chromatography, Liquid; HeLa Cells; Polyribosomes; Processing Bodies; Proteomics; RNA, Messenger; Tandem Mass Spectrometry; Adenine; RNA-Binding Proteins; Protein Biosynthesis
PubMed: 38016476
DOI: 10.1016/j.molcel.2023.10.040 -
Journal of Comparative Physiology. A,... Jul 2023Using odors to find food and mates is one of the most ancient and highly conserved behaviors. Arthropods from flies to moths to crabs use broadly similar strategies to... (Review)
Review
Using odors to find food and mates is one of the most ancient and highly conserved behaviors. Arthropods from flies to moths to crabs use broadly similar strategies to navigate toward odor sources-such as integrating flow information with odor information, comparing odor concentration across sensors, and integrating odor information over time. Because arthropods share many homologous brain structures-antennal lobes for processing olfactory information, mechanosensors for processing flow, mushroom bodies (or hemi-ellipsoid bodies) for associative learning, and central complexes for navigation, it is likely that these closely related behaviors are mediated by conserved neural circuits. However, differences in the types of odors they seek, the physics of odor dispersal, and the physics of locomotion in water, air, and on substrates mean that these circuits must have adapted to generate a wide diversity of odor-seeking behaviors. In this review, we discuss common strategies and specializations observed in olfactory navigation behavior across arthropods, and review our current knowledge about the neural circuits subserving this behavior. We propose that a comparative study of arthropod nervous systems may provide insight into how a set of basic circuit structures has diversified to generate behavior adapted to different environments.
Topics: Animals; Arthropods; Olfactory Pathways; Smell; Odorants; Brain
PubMed: 36658447
DOI: 10.1007/s00359-022-01611-9 -
The Plant Cell Sep 2023Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. Biomolecular...
Biomolecular condensates are membraneless organelle-like structures that can concentrate molecules and often form through liquid-liquid phase separation. Biomolecular condensate assembly is tightly regulated by developmental and environmental cues. Although research on biomolecular condensates has intensified in the past 10 years, our current understanding of the molecular mechanisms and components underlying their formation remains in its infancy, especially in plants. However, recent studies have shown that the formation of biomolecular condensates may be central to plant acclimation to stress conditions. Here, we describe the mechanism, regulation, and properties of stress-related condensates in plants, focusing on stress granules and processing bodies, 2 of the most well-characterized biomolecular condensates. In this regard, we showcase the proteomes of stress granules and processing bodies in an attempt to suggest methods for elucidating the composition and function of biomolecular condensates. Finally, we discuss how biomolecular condensates modulate stress responses and how they might be used as targets for biotechnological efforts to improve stress tolerance.
Topics: Biomolecular Condensates; Proteome
PubMed: 37162152
DOI: 10.1093/plcell/koad127 -
NPJ Parkinson's Disease Oct 2023Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). It is characterized by a progressive loss of dopaminergic... (Review)
Review
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). It is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the formation of Lewy bodies (LBs). Although PD is primarily considered a gray matter (GM) disease, alterations in white matter (WM) have gained increasing attention in PD research recently. Here we review evidence collected by magnetic resonance imaging (MRI) techniques which indicate WM abnormalities in PD, and discuss the correlations between WM changes and specific PD symptoms. Then we summarize transcriptome and genome studies showing the changes of oligodendrocyte (OLs)/myelin in PD. We conclude that WM abnormalities caused by the changes of myelin/OLs might be important for PD pathology, which could be potential targets for PD treatment.
PubMed: 37907554
DOI: 10.1038/s41531-023-00592-z -
Brain Structure & Function Jul 2023The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with... (Review)
Review
The mammillary body (MB) is a component of the extended hippocampal system and many studies have shown that its functions are vital for mnemonic processes. Together with other subcortical structures, such as the anterior thalamic nuclei and tegmental nuclei of Gudden, the MB plays a crucial role in the processing of spatial and working memory, as well as navigation in rats. The aim of this paper is to review the distribution of various substances in the MB of the rat, with a description of their possible physiological roles. The following groups of substances are reviewed: (1) classical neurotransmitters (glutamate and other excitatory transmitters, gamma-aminobutyric acid, acetylcholine, serotonin, and dopamine), (2) neuropeptides (enkephalins, substance P, cocaine- and amphetamine-regulated transcript, neurotensin, neuropeptide Y, somatostatin, orexins, and galanin), and (3) other substances (calcium-binding proteins and calcium sensor proteins). This detailed description of the chemical parcellation may facilitate a better understanding of the MB functions and its complex relations with other structures of the extended hippocampal system.
Topics: Rats; Animals; Mammillary Bodies; Neurochemistry; Anterior Thalamic Nuclei; Amino Acids; Memory, Short-Term
PubMed: 37378855
DOI: 10.1007/s00429-023-02673-4 -
Nucleic Acids Research Sep 2023Two prominent cytoplasmic RNA granules, ubiquitous RNA-processing bodies (PB) and inducible stress granules (SG), regulate mRNA translation and are intimately related....
Two prominent cytoplasmic RNA granules, ubiquitous RNA-processing bodies (PB) and inducible stress granules (SG), regulate mRNA translation and are intimately related. In this study, we found that arsenite (ARS)-induced SG formed in a stepwise process is topologically and mechanically linked to PB. Two essential PB components, GW182 and DDX6, are repurposed under stress to play direct but distinguishable roles in SG biogenesis. By providing scaffolding activities, GW182 promotes the aggregation of SG components to form SG bodies. DEAD-box helicase DDX6 is also essential for the proper assembly and separation of PB from SG. DDX6 deficiency results in the formation of irregularly shaped 'hybrid' PB/SG granules with accumulated components of both PB and SG. Wild-type DDX6, but not its helicase mutant E247A, can rescue the separation of PB from SG in DDX6KO cells, indicating a requirement of DDX6 helicase activity for this process. DDX6 activity in biogenesis of both PB and SG in the cells under stress is further modulated by its interaction with two protein partners, CNOT1 and 4E-T, of which knockdown affects the formation of both PB and also SG. Together, these data highlight a new functional paradigm between PB and SG biogenesis during the stress.
Topics: Cytoplasmic Granules; DEAD-box RNA Helicases; Processing Bodies; RNA; RNA Processing, Post-Transcriptional; Stress Granules; Humans; Cell Line
PubMed: 37427791
DOI: 10.1093/nar/gkad585