A5052532717- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Genetics and Neurodevelopmental Disorders
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Viral Infections and Immunology Research
- Virus-based gene therapy research
- Advanced Biosensing Techniques and Applications
- Supramolecular Chemistry and Complexes
- Viral Infectious Diseases and Gene Expression in Insects
- Telomeres, Telomerase, and Senescence
- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Muscle Physiology and Disorders
- Metal complexes synthesis and properties
- Supramolecular Self-Assembly in Materials
- Synthesis and Biological Evaluation
- Single-cell and spatial transcriptomics
- Molecular Junctions and Nanostructures
Kyoto University
2013-2024
Kumamoto University
2019-2024
RIKEN Center for Biosystems Dynamics Research
2023-2024
RIKEN Center for Integrative Medical Sciences
2023-2024
Neuroscript (United States)
2022
East Asia School of Theology
2020
Graduate School USA
2015-2020
CGG repeat–derived RNA G-quadruplexes accelerate liquid-to-solid transition of FMRpolyG.
Consecutive guanine RNA sequences can adopt quadruple-stranded structures, termed G-quadruplexes (rG4s). Although rG4-forming are abundant in transcriptomes, the physiological roles of rG4s central nervous system remain poorly understood. In present study, proteomics analysis mouse forebrain identified DNAPTP6 as an binding protein with high affinity and selectivity for rG4s. We found that coordinates assembly stress granules (SGs), cellular phase-separated compartments, rG4-dependent...
A G-quadruplex (quadruplex) is a nucleic acid secondary structure adopted by guanine-rich sequences and considered to be relevant various pharmacological biological contexts. Although number of researchers have endeavored discover develop quadruplex-interactive molecules, poor ligand designability originating from topological similarity the skeleton diverse quadruplexes has remained bottleneck for gaining specificity individual quadruplexes. This work reports on hybrid molecules that were...
Abstract Hairpin N ‐methylpyrrole‐ ‐methylimidazole polyamide seco ‐CBI conjugates 2 – 6 were designed for synthesis by Fmoc solid‐phase synthesis, and their DNA‐alkylating activities against the Kras codon 13 mutation compared high‐resolution denaturing gel electrophoresis with 225 base pair (bp) DNA fragments. Conjugate 5 had high reactivity towards site, alkylation occurring at A of sequence 5′‐ACGTCACC ‐3′ (site 2), including minor 1 bp‐mismatch wild type 5′‐ACG C CACC 3). , which...
Abstract Synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by the aggregation of α-synuclein, leading to progressive neurodegeneration 1,2,3,4,5,6,7,8 . However, intracellular mechanism α-synuclein remains unclear. Here we show that assembly RNA G-quadruplexes forming scaffolds for aggregation, contributing neurodegeneration. Purified binds directly through N-terminus. G-quadruplex itself undergoes phase separation Ca 2+ ,...
ATR-X (α-thalassemia/mental retardation X-linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence promoter region α-globin gene cluster. The VNTR sequence, which contains potential G-quadruplex-forming CGC(GGGGCGGGG)n , involved downregulation expression. We investigated G-quadruplex and i-motif formation single-stranded DNA long double-stranded DNA. without showed approximately twofold higher luciferase...
Short tandem repeats are inherently unstable during DNA replication depending on repeat length, and the expansion of length in human genome is responsible for disorders. Pentanucleotide AAGGG ACAGG expansions intron 2 gene encoding factor C subunit 1 (RFC1) cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) other phenotypes late-onset ataxia. Herein, we reveal structural polymorphism RFC1 associated with CANVAS vitro. Single-stranded formed a hybrid-type...
Abstract Tandem repeats of guanine-rich sequences in RNA often form thermodynamically stable four-stranded structures. Such G-quadruplexes have long been considered to be linked essential biological processes, yet their physiological significance cells remains unclear. Here, we report a approach that permits the detection G-quadruplex structures modulate protein translation mammalian cells. The combines antibody arrays and RGB-1, small molecule selectively stabilizes Analysis mRNA products...
Expansion of CAG and CTG (CWG) triplet repeats causes several inherited neurological diseases. The CWG repeat diseases are thought to involve complex pathogenic mechanisms through expanded repeat-derived RNAs in a noncoding region polypeptides coding region, respectively. However, an effective therapeutic approach has not been established for the Here, we show that DNA-targeting compound, cyclic pyrrole-imidazole polyamide (CWG-cPIP), suppressed pathogenesis CWG-cPIP bound hairpin form...
We developed an epigenetically active, cooperative DNA binding transcription factor platform assisted by cucurbit[7]uril (CB7) host-guest modules. This new type of molecule termed ePIP-HoGu not only mimics the operation factors as a pair but also recruits epigenetic modifier to particular locus.
G-quadruplex (G4) DNA is often observed as a secondary structure in guanine-rich sequences, and thought to be relevant pharmacological biological events. Therefore, G4 ligands have attracted great attention potential anticancer therapies or molecular probe applications. Here, we designed cyclic imidazole/lysine polyamide (cIKP) new class of ligand. It was readily synthesized without time-consuming column chromatography. cIKP selectively recognized particular structures with low nanomolar...
Synthetic molecules capable of DNA binding and mimicking cooperation transcription factor (TF) pairs have long been considered a promising tool for manipulating gene expression. Our previously reported Pip-HoGu system, programmable binder pyrrole-imidazole polyamides (PIPs) conjugated to host-guest moiety, defined general framework cooperative TF pair-DNA interactions. Here, we supplanted the modules with left-handed (LH) γPNA modules: i.e., PIPs nucleic acid-based system (Pip-NaCo). LH was...
Abstract Many long pyrrole‐imidazole polyamides (PIPs) have been synthesized in the search for higher specificity, with aim of realizing great potential such compounds biological and clinical areas. Among several types PIPs, we designed hairpin cyclic PIPs targeting identical sequences. Bind‐n‐Seq analysis revealed that both bound to intended However, adenines data analyzed by previously reported method appeared be significantly motif ratio than thymines, even though were not expected...
The G-quadruplex (G4) is one type of higher-order structure nucleic acids and thought to play important roles in various biological events such as regulation transcription inhibition DNA replication. Pyrrole-imidazole polyamides (PIPs) are programmable small molecules that can sequence-specifically bind with high affinity the minor groove double-stranded (dsDNA). Herein, we designed head-to-head hairpin PIP dimers their target dsDNA a model G4-forming sequence. Using an electrophoresis...
We report the photochemistry of (Br)U substituted DNA as a versatile platform to investigate binding sites pyrene conjugated pyrrole imidazole polyamides (PIPs). The results suggest that approach can be used on routine basis for screening polyamide sites.
Pyrrole-imidazole polyamides (PIPs) bind to predetermined double-stranded DNA sequences and selectively target a large variety of sequences. Although the forward-binding (5'-3'/N-C) orientation, in which N-terminus PIPs faces 5'-terminus DNAs, is considered be main binding manner PIPs, reverse-binding (5'-3'/C-N) C-terminus 3'-terminus sometimes causes unintended binding. Here, we synthesized optical or structural isomers previously reported cyclic (cPIPs), differ position amino groups...