A5102946953- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Amyotrophic Lateral Sclerosis Research
- RNA regulation and disease
- Cancer-related gene regulation
- RNA Interference and Gene Delivery
- Prion Diseases and Protein Misfolding
- Genetic Neurodegenerative Diseases
- Ubiquitin and proteasome pathways
- Neurological diseases and metabolism
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Biochemical and Structural Characterization
- Nuclear Structure and Function
- Protein Structure and Dynamics
- Molecular Biology Techniques and Applications
- Calcium signaling and nucleotide metabolism
- MXene and MAX Phase Materials
- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- Phosphodiesterase function and regulation
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Peptidase Inhibition and Analysis
Nagoya City University
2012-2024
University of Rochester
2005-2008
The University of Tokyo
1999-2003
In eukaryotes, shortening of the 3′-poly(A) tail is rate-limiting step in degradation most mRNAs, and two major mRNA deadenylase complexes—Caf1–Ccr4 Pan2–Pan3—play central roles this process, referred to as deadenylation. However, molecular mechanism triggering deadenylation remains elusive. Previously, we demonstrated that eukaryotic releasing factor eRF3 mediates decay a manner coupled translation termination. Here, report The eRF3-mediated catalyzed by both Caf1–Ccr4 Pan2–Pan3....
Messenger RNA decay, which is a regulated process intimately linked to translation, begins with the deadenylation of poly(A) tail at 3' end. However, precise mechanism triggering first step mRNA decay and its relationship translation have not been elucidated. Here, we show that termination factor eRF3 mediates in yeast Saccharomyces cerevisiae. The N-domain eRF3, necessarily required for termination, interacts poly(A)-binding protein PABP. When this interaction blocked by means deletion or...
In yeast, aberrant mRNAs lacking in-frame termination codons are recognized and degraded by the non-stop decay (NSD) pathway. The recognition of involves a member eRF3 family GTP-binding proteins, Ski7. Ski7 is thought to bind ribosome stalled at 3'-end mRNA poly(A) tail recruit exosome degrade message. However, not found in mammalian cells, even presence NSD mechanism itself has remained enigmatic. Here, we show that unstable translation-dependent manner cells. requires another (Hbs1), its...
In mammalian cells, poly(A) binding protein C1 (PABP C1) has well-known roles in mRNA translation and decay the cytoplasm. However, PABPC1 also shuttles out of nucleus, its nuclear function is unknown. Here, we show that PABPC1, like major PABPN1, associates with pre-mRNAs are polyadenylated intron containing. does not bind nonpolyadenylated histone mRNA, indicating interaction pre-mRNA requires a tail. Consistent this conclusion, UV cross-linking results obtained using intact cells reveal...
Translation of 5′ terminal oligopyrimidine (TOP) mRNAs encoding the protein synthesis machinery is strictly regulated by an amino-acid-sensing mTOR pathway. However, its regulatory mechanism remains elusive. Here, we demonstrate that TOP mRNA translation positively correlates with poly(A) tail length under active/amino-acid-rich conditions, suggesting are post-transcriptionally controlled tail-length regulation. Consistent this, dynamically fluctuates in response to amino acid availability....
The 2'-5'-oligoadenylate synthetase (OAS)/RNase L pathway is an innate immune system that protects hosts against pathogenic viruses and bacteria through cleavage of exogenous single-stranded RNA; however, this system's selective targeting mechanism remains unclear. Here, we identified mRNA quality control factor Dom34 as a novel restriction for positive-sense RNA virus. Downregulation RNase increases viral replication, well half-life the RNA. directly binds to form surveillance complex...
The RNA-binding protein Ataxin-2 binds to and stabilizes a number of mRNA sequences, including that the transactive response DNA-binding 43 kDa (TDP-43). is additionally involved in several processes requiring translation, such as germline formation, long-term habituation, circadian rhythm formation. However, it has yet be unambiguously demonstrated actually activating translation its target mRNAs. Here we provide direct evidence from polysome profile analysis showing enhances Our recently...
Eukaryotic mature mRNAs possess a poly adenylate tail (poly(A)), to which multiple molecules of poly(A)-binding protein C1 (PABPC1) bind. PABPC1 regulates translation and mRNA metabolism by binding regulatory proteins. To understand functional mechanism the proteins, it is necessary reveal how exist on poly(A). Here, we characterize structure poly(A), using transmission electron microscopy (TEM), chemical cross-linking, NMR spectroscopy. The TEM images cross-linking results indicate that...
In this study, we devised a novel method to create heterologous producers of lethal antibiotics against host bacteria. Heterologous cannot be created when are toxic To overcome challenge, developed involving construction combinatorial library with various promoters and screening based on the production. realize this, utilized Combi-OGAB (Combinatorial Ordered Gene Assembly in Bacillus subtilis), which technology can effectively construct diverse accelerate procedures. B. subtilis Gramicidin...
Abstract Stress induces global stabilization of the mRNA poly(A) tail (PAT) and assembly untranslated poly(A)-tailed into mRNPs that accumulate in stress granules (SGs). While mechanism behind stress-induced PAT has recently emerged, biological significance under remains elusive. Here, we demonstrate is a prerequisite for SG formation. Perturbations length impact formation; shortening, achieved by overexpressing deadenylases, inhibits formation, whereas lengthening, their dominant negative...
Eukaryotic releasing factor GSPT/eRF3 mediates translation termination-coupled mRNA decay via interaction with a cytosolic poly(A)-binding protein (PABPC1). A region of eRF3 containing two overlapping PAM2 (PABPC1-interacting motif 2) motifs is assumed to bind the PABC domain PABPC1, on poly(A) tail mRNA. are also found in major deadenylases Caf1-Ccr4 and Pan2-Pan3, whose activities enhanced upon PABPC1 binding these motifs. Their deadenylase regulated by eRF3, which competitively prevent...
TAR DNA-binding protein 43 (TDP-43) is an RNA-binding protein, whose loss-of-function mutation causes amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Recent studies demonstrated that TDP-43 binds to the 3' untranslated region (UTR) of target mRNAs promote mRNA instability. Here, we show recruits Caf1 deadenylase targets accelerates their deadenylation. Tethering 3'UTR recapitulates destabilization mRNA, This accelerated deadenylation inhibited by a dominant...
Translation termination-coupled deadenylation is the first and often rate-limiting step of eukaryotic mRNA decay in which two deadenylases, Ccr4-Caf1 Pan2, play key roles. One Caf1, associates with Tob, recruits Caf1 to poly(A) tail through interactions a cytoplasmic poly(A)-binding protein 1 (PABPC1). We previously proposed that competition between Tob eRF3 (a translation termination factor interacts PABPC1) responsible for regulation deadenylase activity. However, molecular mechanism...
PC‐1 is a type II membrane‐bound glycoprotein consisting of short N‐terminal cytoplasmic domain and large C‐terminal extracellular domain, which contains phosphodiesterase/pyrophosphatase activity. When Jurkat T cells were cultured with dibutyryl cAMP, the its soluble form induced. They purified as homodimer 130 kDa peptide 120 monomer, respectively, same two forms could also be obtained from COS‐7 that had been transfected cDNA. The indistinguishable each other in terms their enzyme...
Eukaryotic mRNAs possess a poly(A) tail at their 3'-end, to which poly(A)-binding protein C1 (PABPC1) binds and recruits other proteins that regulate translation. Enhanced poly(A)-dependent translation, is also PABPC1 dependent, promotes cellular viral proliferation. PABP-interacting 2A (Paip2A) effectively represses translation by causing the dissociation of from tail; however, underlying mechanism remains unknown. This study was conducted investigate functional mechanisms Paip2A action...