A5015429318- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Fungal and yeast genetics research
- Genetics and Neurodevelopmental Disorders
- Cancer-related gene regulation
- Viral Infections and Immunology Research
- Mitochondrial Function and Pathology
- Plant and Fungal Interactions Research
- Cancer-related molecular mechanisms research
- Amino Acid Enzymes and Metabolism
- Food Quality and Safety Studies
- Parkinson's Disease Mechanisms and Treatments
- Plant Disease Resistance and Genetics
- Plant Disease Management Techniques
- ATP Synthase and ATPases Research
- Veterinary medicine and infectious diseases
- Photosynthetic Processes and Mechanisms
- Ubiquitin and proteasome pathways
- Plant Virus Research Studies
- Redox biology and oxidative stress
Nagoya City University
2022-2023
Tohoku University
2017-2021
Nagoya University
2013-2017
Kansas State University
2006-2013
University of Massachusetts Chan Medical School
2012-2013
Institut thématique Génétique, génomique et bioinformatique
2013
Manhattan High School
2013
University of Tsukuba
2011
Tokyo University of Agriculture and Technology
2001-2005
The University of Tokyo
2004
Translation arrest by polybasic sequences induces ribosome stalling, and the product is degraded ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of 40S ribosomal protein uS10 E3 ubiquitin ligase Hel2 (or RQT1) required for RQC. We identify a RQC-trigger (RQT) subcomplex composed RNA helicase-family Slh1/Rqt2, ubiquitin-binding Cue3/Rqt3, yKR023W/Rqt4 The defects in RQC RQT mutants correlate with sensitivity to anisomycin, which stalls at rotated form....
Ribosome movement is not always smooth and rather often impeded. For ribosome pauses, fundamental issues remain to be addressed, including where ribosomes pause on mRNAs, what kind of RNA/amino acid sequence causes this pause, the physiological significance attenuation protein synthesis. Here, we survey positions collisions caused by pauses in humans zebrafish using modified profiling. Collided ribosomes, i.e., disomes, emerge at various sites: Pro-Pro/Gly/Asp motifs; Arg-X-Lys stop codons;...
Abstract FUS is an RNA/DNA-binding protein involved in multiple steps of gene expression and associated with amyotrophic lateral sclerosis (ALS) fronto-temporal lobar degeneration (FTLD). However, the specific disease-causing and/or modifying mechanism mediated by largely unknown. Here we evaluate intrinsic roles on synaptic functions animal behaviours. We find that depletion downregulates GluA1, a subunit AMPA receptor. binds GluA1 mRNA vicinity 3′ terminus controls poly (A) tail...
MicroRNAs (miRNAs) are small, noncoding RNAs that inhibit translation and promote mRNA decay. The levels of mature miRNAs the result different rates transcription, processing, turnover. noncanonical polymerase Gld2 has been implicated in stabilization miR-122, possibly through catalyzing 3' monoadenylation; however, there is little evidence this relationship one cause effect. Here, we biochemically characterize Gld2's involvement miRNA monoadenylation its effect on stability. We find...
Highlights•The nuclear interaction between FUS and SFPQ is affected by disease mutations•FUS/SFPQ regulate tau isoforms altering skipping of Mapt exon 10•Silencing or in adult mice induces FTLD-like phenotypes•Co-silencing 4R-T rescues the phenotypes FUS/SFPQ-silenced miceSummaryFused sarcoma (FUS) splicing factor, proline- glutamine-rich (SFPQ) are RNA binding proteins that metabolism. We found alternative gene at 10, which generates 4-repeat (4R-T) 3-repeat (3R-T), regulated interactions...
Highlights•FUS regulates post-synaptic density protein interaction and PSD-95 localization•3′UTR length-dependent control of SynGAP α2 by FUS is critical for spine maturation•FUS, together with ELAVL proteins, controls mRNA stability at its 3′UTR•SynGAP supplementation ameliorates behavioral aberrations in FUS-knockout miceSummaryFUS an RNA-binding associated frontotemporal lobar degeneration (FTLD) amyotrophic lateral sclerosis (ALS). Previous reports have demonstrated intrinsic roles...
Ribosome-associated quality control (RQC) relieves stalled ribosomes and eliminates potentially toxic nascent polypeptide chains (NCs) that can cause neurodegeneration. During RQC, RQC2 modifies NCs with a C-terminal alanine threonine (CAT) tail. CAT tailing promotes ubiquitination of for proteasomal degradation, while RQC failure in budding yeast disrupts proteostasis via CAT-tailed NC aggregation. However, the tail its cytotoxicity mammals have remained largely uncharacterized. We...
In eubacteria, the dissociation of 70 S ribosome into 30 and 50 subunits is essential first step for translation initiation canonical mRNAs that possess 5′-leader sequences. However, a number leaderless start with codon have been identified in some eubacteria. These shown to be translated efficiently vivo. Here we investigated process by which mRNA initiated using highly reconstituted cell-free system from Escherichia coli. We found bind preferentially ribosomes mRNA·70 S·fMet-tRNA complex...
Apoptosis signal-regulating kinase 1 (ASK1) is an oxidative stress-responsive that regulated by various interacting molecules and post-translational modifications. However, how these modifications cooperatively regulate ASK1 activity remains largely unknown. Here, we showed tripartite motif 48 (TRIM48) orchestrates the regulation of stress-induced activation. A pull-down screen identified a TRIM48-interacting partner, protein arginine methyltransferase (PRMT1), which negatively regulates...
TDP‐43 and FUS are linked to amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD), loss of function either protein contributes these neurodegenerative conditions. To elucidate the TDP‐43‐ FUS‐regulated pathophysiological RNA metabolism cascades, we assessed differential gene expression alternative splicing profiles related regulation by or in primary cortical neurons. These overlapped >25% with respect >9% splicing. The shared downstream targets may form a...
FUS is genetically and pathologically linked to amyotrophic lateral sclerosis (ALS) frontotemporal lobar degeneration (FTLD). To clarify the RNA metabolism cascade regulated by in ALS/FTLD, we compared FUS-regulated transcriptome profiles different lineages of primary cells from central nervous system. The FUS-mediated gene expression alternative splicing motor neurons were similar those cortical neurons, but not cerebellar despite similarity innate signature. glial neurons. We identified...
eIF2α phosphorylation-mediated translational regulation is crucial for global translation repression by various stresses, including the unfolded protein response (UPR). However, control during UPR has not been demonstrated in yeast. This study investigated ribosome ubiquitination-mediated controls UPR. Tunicamycin-induced ER stress enhanced levels of ubiquitination ribosomal proteins uS10, uS3 and eS7. Not4-mediated monoubiquitination eS7A was required resistance to tunicamycin, whereas E3...
TAR DNA-binding protein of 43 kDa (TDP-43) plays a major role in the pathogenesis frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Although pathological continuity between FTLD ALS has been suggested, neuropathological changes lower motor neuron (LMN) systems have not assessed TDP-43-associated (FTLD-TDP), to our knowledge.To investigate FTLD-TDP by comparing their respective system.A retrospective clinical medical record review semiquantitative evaluation...
int-6 is one of the frequent integration sites for mouse mammary tumor viruses. Although its product e-subunit translation initiation factor eIF3, other evidence indicates that it interacts with proteasomes or proteins to regulate protein stability. Here we report fission yeast int6(+) required overcoming stress imposed by histidine starvation, using drug 3-aminotriazole (3AT). Microarray and complementary Northern studies wild-type, int6Delta gcn2Delta mutants indicate 3AT-treated wild-type...
In eukaryotes, the 40 S ribosomal subunit serves as platform of initiation factor assembly, to place itself precisely on AUG start codon. Structural arrangement 18 rRNA determines overall shape subunit. Here, we present genetic evaluation yeast function using 10 point mutations altering polysome profile. All mutants reduce abundance mutant S, making it limiting for translation initiation. Two isolated mutations, G875A, core domain that binds eIF1 and eIF2, A1193U, changing h31 loop located...
RNA-dependent RNA polymerase (RdRp) activity was detected in the crude microsomal fraction of rice cultured cells that contain a 14 kbp double-stranded (dsRNA). RdRp is maximal presence all four nucleotide triphosphates and Mg2+ ion resistant to inhibitors DNA-dependent polymerases (actinomycin D α-amanitin). increases approximately 2.5-fold 0.5% deoxycholate. Treatment purified with proteinase K plus deoxycholate suggests enzyme complex its own kb template located vesicles. The solubilized...