Tatsuaki Kurosaki

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Nonsense-mediated mRNA decay (NMD) controls the quality of eukaryotic gene expression and also degrades physiologic mRNAs. How NMD targets are identified is incompletely understood. A central NMD factor is the ATP-dependent RNA helicase upframeshift 1 (UPF1). Neither the distance in space between the termination codon and the poly(A) tail nor the binding of(More)
Nonsense-mediated mRNA decay (NMD), which degrades transcripts harboring a premature termination codon (PTC), depends on the helicase up-frameshift 1 (UPF1). However, mRNAs that are not NMD targets also bind UPF1. What governs the timing, position, and function of UPF1 binding to mRNAs remains unclear. We provide evidence that (i) multiple UPF1 molecules(More)
Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that typifies all eukaryotes examined to date. NMD surveys newly synthesized mRNAs and degrades those that harbor a premature termination codon (PTC), thereby preventing the production of truncated proteins that could result in disease in humans. This is evident from dominantly(More)
Myotonic dystrophy type 2 (DM2) is a subtype of the myotonic dystrophies, caused by expansion of a tetranucleotide CCTG repeat in intron 1 of the zinc finger protein 9 (ZNF9) gene. The expansions are extremely unstable and variable, ranging from 75-11,000 CCTG repeats. This unprecedented repeat size and somatic heterogeneity make molecular diagnosis of DM2(More)
We investigated the CAG repeat sequence of the spinocerebellar ataxia type 1 (SCA1) gene in various species of primates to reveal how human has acquired the repeat structure with interruptions. Our results demonstrate no repetitive structure in the region corresponding to the human CAG repeats in prosimians and New World monkeys like in rodents, perfect(More)
Human PQBP-1 is known to interact with triplet repeat disease gene products such as ataxin and huntingtin through their poly-glutamine (poly-Q) tracts. The poly-Q tracts show extensive variation in both the number and the configuration of repeats among species. A surface plasmon resonance assay showed clear interaction between human PQBP-1 and Q11,(More)
Limb-girdle muscular dystrophy (LGMD) is genetically one of the most heterogeneous diseases, with 420 genes identified.1 Moreover, causative mutations remain undetermined in more than half of all LGMD patients, suggesting additional heterogeneity. In Japan for instance, B60% of the genetic causes of LGMD remain unknown (YK Hayashi et al., unpublished data).(More)
Spinocerebellar ataxia type 10 is caused by ATTCT repeat expansion in the ATXN10 gene in humans. We studied the evolutionary history of the human genome to determine the time and mechanism of the acquisition of unstable ATTCT repeats in the genome. We found that long interspersed element-1 (LINE-1) was inserted into ATXN10 intron 9; Alu was then inserted in(More)
Brain-2 (Brn-2), a Class III POU transcription factor, plays an important role in the development of the neocortex and the establishment of neural cell lineage. Here we performed a yeast two-hybrid screening to identify the Brn-2 binding proteins. We obtained Jun-activation-domain-binding protein 1 (Jab1) as a new Brn-2 binding protein. Direct interaction(More)
Sirs, Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant neurodegenerative disorder characterized by a unique combination of progressive ataxia and seizures. The mutation causing SCA10 is an unstable and massive expansion (800∼4500 repeats; unaffected range, 10–29) of an ATTCT pentanucleotide repeat in intron 9 of the ataxin10 (ATXN10) gene on(More)