A5082046242- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Wnt/β-catenin signaling in development and cancer
- Cancer-related molecular mechanisms research
- Cancer-related gene regulation
- Tissue Engineering and Regenerative Medicine
- Genomics and Chromatin Dynamics
- Herpesvirus Infections and Treatments
- Innovative Microfluidic and Catalytic Techniques Innovation
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Organ Transplantation Techniques and Outcomes
- Immune Cell Function and Interaction
- Liver physiology and pathology
- Microfluidic and Capillary Electrophoresis Applications
- Reproductive biology and impacts on aquatic species
- Electrospun Nanofibers in Biomedical Applications
- Viral Infections and Immunology Research
- Aquaculture Nutrition and Growth
- 3D Printing in Biomedical Research
- Genetics and Neurodevelopmental Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- RNA Interference and Gene Delivery
National Institute of Advanced Industrial Science and Technology
2014-2024
National Cancer Research Institute
2024
Tokyo Medical and Dental University
2013
The University of Tokyo
2000-2011
California Institute of Technology
2005
Hokkaido University
2004
Institut de Biologie Moléculaire et Cellulaire
2004
National Institute for Basic Biology
2000
Osaka University
2000
Gunma University
2000
Wnt signaling has an important role in both embryonic development and tumorigenesis. β-Catenin, a key component of the pathway, interacts with TCF/LEF family transcription factors activates target genes. Here, we identify novel β-catenin-interacting protein, ICAT, that was found to inhibit interaction β-catenin TCF-4 represses β-catenin–TCF-4-mediated transactivation. Furthermore, ICAT inhibited Xenopus axis formation by interfering signaling. These results suggest negatively regulates via...
The type III-E CRISPR-Cas7-11 effector binds a CRISPR RNA (crRNA) and the putative protease Csx29 catalyzes crRNA-guided cleavage. We report cryo-electron microscopy structures of Cas7-11-crRNA-Csx29 complex with without target (tgRNA), demonstrate that tgRNA binding induces conformational changes in Csx29. Biochemical experiments revealed tgRNA-dependent cleavage accessory protein Csx30 by Reconstitution system bacteria showed yields toxic fragments cause growth arrest, which is regulated...
ABSTRACT The enzyme aromatase P-450 (P450arom) catalyses the conversion of androgen to oestrogen. A cDNA insert encoding P450arom was isolated from a rainbow trout ( Oncorhynchus mykiss ) ovary library. sequenced and found contain an open-reading frame predicted encode protein 522 amino acid residues. deduced polypeptide is 52% homologous with human, mouse rat 53% that chicken. confirmed by introducing it into COS-1 monkey kidney tumour cells (COS-1 cells) detecting testosterone...
The Wnt signaling pathway is activated in most human colorectal tumors. Mutational inactivation the tumor suppressor adenomatous polyposis coli (APC), as well activation of β-catenin, causes accumulation which turn associates with T cell factor/lymphoid enhancer factor (TCF/LEF) family transcription factors and activates their target genes. Here we show that β-catenin BMP activin membrane-bound inhibitor (BAMBI)/NMA gene. expression level BAMBI was found to be aberrantly elevated...
A poly(A) tail functions in mRNA turnover and facilitating translation as a ribonucleoprotein complex with binding proteins (PABPs). However, factors that associate the other than PABPs have not been described. Using proteomics, we identified candidate interact to 3' terminus of tail. Among these proteins, focused on La motif-related protein 1 (LARP1) found LARP1 specifically recognizes termini normal tails. We also reveal stabilizes multiple mRNAs carrying 5' terminal oligopyrimidine tract...
Abstract Low-density lipoprotein receptor (LDLR) mRNA is unstable, but stabilized upon extracellular signal-regulated kinase (ERK) activation, possibly through the binding of certain proteins to LDLR 3′-untranslated region (UTR), although detailed mechanism underlying this stability control unclear. Here, using a proteomic approach, we show that ZFP36L1 and ZFP36L2 specifically bind 3′-UTR recruit CCR4-NOT-deadenylase complex, resulting in destabilization. We also C-terminal regions are...
Destabilization of Atg7 mRNA by the CCR4-NOT complex prevents p53-dependent cell death in heart.
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...
Uncoupling protein 1 (Ucp1) contributes to thermogenesis, and its expression is regulated at the transcriptional level. Here, we show that Ucp1 also post-transcriptionally. In inguinal white adipose tissue (iWAT) of mice fed a high-fat diet (HFD), level decreases concomitantly with increases in Cnot7 interacting partner Tob. HFD-fed lacking Tob express elevated levels mRNA iWAT are resistant diet-induced obesity. has an elongated poly(A) tail persists Cnot7(-/-) and/or Tob(-/-) on HFD....
Abstract Wnt signaling plays a crucial role in number of developmental processes and tumorigenesis. β-Catenin is stabilized by associates with the TCF/LEF family transcription factors, thereby activating target genes. Constitutive activation β-catenin-TCF–mediated resulting from mutations adenomatous polyposis coli (APC), β-catenin, or Axin believed to be critical step tumorigenesis among divergent types cancers. Here we show that transactivation potential β-catenin-TCF complex enhanced its...
The CCR4-NOT deadenylase complex plays crucial roles in mRNA decay and translational repression induced by poly(A) tail shortening. Although the vitro activities of each component this have been well characterized, its vivo role immune cells remains unclear. Here we show that mice lacking CNOT3 subunit complex, specifically B cells, a developmental block at pro- to pre-B cell transition. regulated generation germline transcripts VH region immunoglobulin heavy chain (Igh) locus, compaction...
Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed lncRNA DAPALR 5´ UTR Doublesex1 ( Dsx1 ), male determining gene in Daphnia magna . By affinity purification, we identified an RNA binding protein, Shep as a protein. also binds to by recognizing sequence suppresses translation mRNA. In vitro vivo analyses indicated that increased efficiency sequestration Shep. This...
In the canonical Wnt signaling pathway, translocation of β-catenin is important for activation target genes in nucleus. However, molecular mechanisms underlying its nuclear localization remain unclear. present study, we found IQGAP1 to be a regulator function via importin-β5. Xenopus embryos, depletion reduced Wnt-induced accumulation and expression during early embryogenesis. Depletion endogenous importin-β5 associated with also β-catenin. Moreover, small GTPase, Ran1, contributes genes....
Abstract The CCR4-NOT complex is conserved in eukaryotes and involved mRNA metabolism, though its molecular physiological roles remain to be established. We show here that CNOT3-depleted mouse embryonic fibroblasts (MEFs) undergo cell death. Levels of other subunits are decreased MEFs. death phenotype rescued by introduction wild-type (WT), but not mutated CNOT3 suppressed the pan-caspase inhibitor, zVAD-fluoromethylketone. Gene expression profiling reveals mRNAs encoding death-related...
Hepatocyte transplantation (HCT) is a potential bridging therapy or an alternative to liver transplantation. Conventionally, single-cell hepatocytes are injected via the portal vein. This strategy, however, has yet overcome poor cell engraftment and function. Therefore, we developed orthotopic HCT method using liver-derived extracellular matrix (L-ECM) gel. PXB cells (flesh mature human hepatocytes) were dispersed into hydrogel solution in vitro, gel was immediately gelated 37°C incubators...
Abstract Background In an extensive genomic analysis of lung adenocarcinomas (LUADs), driver mutations have been recognized as potential targets for molecular therapy. However, there remain cases where target genes are not identified. Super-enhancers and structural variants frequently identified in several hundred loci per case. Despite this, most cancer research has approached the these data sets separately, without merging comparing data, no examples integrated LUAD. Methods We performed...
Histone gene expression is tightly coordinated with DNA replication, as it activated at the onset of S phase and suppressed end phase. Replication-dependent histone precisely controlled both transcriptional posttranscriptional levels. U7 small nuclear ribonucleoprotein (U7 snRNP) involved in 3′-end processing nonpolyadenylated mRNAs, which required for phase-specific expression. The present study reports a unique function snRNP repression transcription under cell cycle-arrested conditions....