A5002596337- RNA regulation and disease
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- Viral Infections and Vectors
- Photoreceptor and optogenetics research
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Neural dynamics and brain function
- PI3K/AKT/mTOR signaling in cancer
- Neuroscience and Neuropharmacology Research
- Vector-Borne Animal Diseases
- Academic Writing and Publishing
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Cancer-related molecular mechanisms research
- Biochemical and Structural Characterization
- Polyamine Metabolism and Applications
- Insect and Pesticide Research
- Enzyme Structure and Function
RIKEN Center for Biosystems Dynamics Research
2018-2024
CLS Technology (Norway)
2017
The University of Tokyo
2014-2016
Systems Biology Institute
2014
The small molecule ISRIB antagonizes the activation of integrated stress response (ISR) by phosphorylated translation initiation factor 2, eIF2(αP). and eIF2(αP) bind distinct sites in their common target, eIF2B, a guanine nucleotide exchange for eIF2. We have found that ISRIB-mediated acceleration eIF2B's activity vitro is observed preferentially presence attenuated mutations desensitize eIF2B to inhibitory effect ISRIB's efficacy as an ISR inhibitor cells also depends on Cryoelectron...
Integrated stress response on the brain During translation, regulation of protein synthesis by phosphorylation eukaryotic translation initiation factor 2 (eIF2) is a common consequence diverse stimuli, which leads to reprogramming gene expression. This process, known as integrated response, one most fundamental mechanisms translational control conserved throughout eukaryotes. It also promising therapeutic target in neurodegenerative diseases and traumatic injury. Kashiwagi et al. report...
Abstract Various stressors such as viral infection lead to the suppression of cap-dependent translation and activation integrated stress response (ISR), since stress-induced phosphorylated eukaryotic initiation factor 2 [eIF2(αP)] tightly binds eIF2B prevent it from exchanging guanine nucleotide molecules on its substrate, unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this through interaction between nonstructural protein NSs host eIF2B. However, precise mechanism has...
Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a substrate. However, limited number of enzymes responsible for this modification have been reported. Moreover, the biological role has remained poorly understood to date. Here, we report that human METTL18 is methyltransferase ribosomal protein RPL3 specifically slows ribosome traversal Tyr codons, allowing proper folding synthesized proteins. By performing an in vitro assay with methyl...
Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, mechanism by which conformational pump an anion to achieve unidirectional transport, from extracellular side cytoplasmic side, anion-pumping remains enigmatic. We collected...
Vanishing white matter disease (VWM) is an autosomal recessive neurological disorder caused by mutation(s) in any subunit of eukaryotic translation initiation factor 2B (eIF2B), activator eIF2. VWM occurs with mutation the genes encoding eIF2B subunits (EIF2B1, EIF2B2, EIF2B3, EIF2B4, and EIF2B5). However, little known regarding underlying pathogenetic mechanisms or how to treat patients VWM. Here we describe identification detailed analysis a new spontaneous mutant mouse harboring point...
The eukaryotic translation initiation factor 2A (eIF2A) was identified as a that stimulates the binding of methionylated initiator tRNA (Met-tRNA i (Met) ) to 40S ribosomal subunit, but its physiological role remains poorly defined. Recently, eIF2A shown be involved in unconventional from CUG codons and viral protein synthesis under stress conditions where eIF2 is inactivated. We determined crystal structure WD-repeat domain Schizosaccharomyces pombe at 2.5 Å resolution. adopts novel...
Tight control of protein synthesis is necessary for cells to respond and adapt environmental changes rapidly. Eukaryotic translation initiation factor (eIF) 2B, the guanine nucleotide exchange eIF2, a key target at step. The activity eIF2B inhibited by stress-induced phosphorylation eIF2. As result, level active GTP-bound eIF2 lowered, attenuated. large multi-subunit complex composed five different subunits, all subunits are gene products responsible neurodegenerative disease,...
Abstract Protein methylation occurs predominantly on lysine and arginine residues, but histidine also serves as a substrate for the modification. However, limited number of enzymes responsible this modification have been reported. Moreover, biological role has remained poorly understood. Here, we report that human METTL18 is methyltransferase ribosomal protein RPL3 specifically slows ribosome traverse tyrosine codons, allowing proper folding synthesized proteins. By performing an in vitro...
Abstract The small molecule ISRIB antagonises the activation of integrated stress response (ISR) by phosphorylated translation initiation factor 2, eIF2(αP). and eIF2(αP) bind distinct sites in their common target, eIF2B, a guanine nucleotide exchange (GEF) for eIF2. We have found that ISRIB-mediated acceleration eIF2B activity vitro is observed preferentially presence attenuated mutations desensitise to inhibitory effects ISRIB’s efficacy as an ISR inhibitor cells also depends on Cryo-EM...
eIF2B (eukaryotic initiation factor 2B) is a key regulator of translation initiation. It catalyzes guanine nucleotide exchange on eIF2, which delivers the methionylated initiator tRNA to 40S ribosomal subunit. This reaction inhibited by stress-induced phosphorylation eIF2 alpha subunit, leads global repression cellular protein synthesis. composed five subunits. The catalytic gamma/epsilon subcomplex responsible for exchange, while regulatory alpha/beta/delta discriminates status We...
Abstract A core event in the integrated stress response, an adaptive pathway common to all eukaryotic cells response various stimuli, is phosphorylation of translation initiation factor 2 (eIF2). Normally, unphosphorylated eIF2 transfers methionylated initiator tRNA ribosome a GTP-dependent manner. In contrast, phosphorylated inhibits its specific guanine nucleotide exchange eIF2B, which leads deficiency active and resultant global repression. To unveil mechanism by status regulates eIF2B...
SUMMARY Various stressors such as viral infection lead to the suppression of cap-dependent translation and activation integrated stress response (ISR), since stress-induced phosphorylated eukaryotic initiation factor 2 [eIF2(αP)] tightly binds eIF2B prevent it from exchanging guanine nucleotides on unphosphorylated eIF2. Sandfly fever Sicilian virus (SFSV) evades this through interaction between its nonstructural protein NSs host eIF2B. Our cryo-electron microscopy (cryo-EM) analysis...
Abstract Eukaryotic translation initiation factor (eIF) 4A — a DEAD-box RNA-binding protein plays an essential role in initiation. Two mammalian eIF4A paralogs, eIF4A1 and eIF4A2, have been assumed to be redundant because of their high homology, the difference functions has poorly understood. Here, we show that eIF4A1, but not enhances translational repression during inhibition mechanistic target rapamycin complex 1 (mTORC1), kinase controlling cell proliferation. RNA-immunoprecipitation...
ABSTRACT Light-driven chloride-pumping rhodopsins actively transport anions, including various halide ions, across cell membranes. Recent studies using time-resolved serial femtosecond crystallography (TR-SFX) have uncovered the structural changes and ion transfer mechanisms in light-driven cation-pumping rhodopsins. However, mechanism by which conformational pump an anion to achieve unidirectional transport, from extracellular side cytoplasmic side, anion-pumping remains enigmatic. We...