UECHI Tamayo



Faculty of Medicine School of Medicine


Associate Professor

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Degree 【 display / non-display

  • 博士(医学) ( 2003.3   琉球大学 )

Research Areas 【 display / non-display

  • Life Science / Hematology and medical oncology  / 先天性貧血


Papers 【 display / non-display

  • Cytosolic dsDNA of mitochondrial origin induces cytotoxicity and neurodegeneration in cellular and zebrafish models of Parkinson’s disease Reviewed

    Matsui H., Ito J., Matsui N., Uechi T., Onodera O., Kakita A.

    Nature Communications   12 ( 1 )   2021.5

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Nature Communications  

    Mitochondrial dysfunction and lysosomal dysfunction have been implicated in Parkinson’s disease (PD), but the links between these dysfunctions in PD pathogenesis are still largely unknown. Here we report that cytosolic dsDNA of mitochondrial origin escaping from lysosomal degradation was shown to induce cytotoxicity in cultured cells and PD phenotypes in vivo. The depletion of PINK1, GBA and/or ATP13A2 causes increases in cytosolic dsDNA of mitochondrial origin and induces type I interferon (IFN) responses and cell death in cultured cell lines. These phenotypes are rescued by the overexpression of DNase II, a lysosomal DNase that degrades discarded mitochondrial DNA, or the depletion of IFI16, which acts as a sensor for cytosolic dsDNA of mitochondrial origin. Reducing the abundance of cytosolic dsDNA by overexpressing human DNase II ameliorates movement disorders and dopaminergic cell loss in gba mutant PD model zebrafish. Furthermore, IFI16 and cytosolic dsDNA puncta of mitochondrial origin accumulate in the brain of patients with PD. These results support a common causative role for the cytosolic leakage of mitochondrial DNA in PD pathogenesis.

    DOI: 10.1038/s41467-021-23452-x


  • Prokaryotic ribosomal RNA stimulates zebrafish embryonic innate immune system Reviewed

    Basu A., Yoshihama M., Uechi T., Kenmochi N.

    BMC Research Notes   13 ( 1 )   2020.1

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMC Research Notes  

    Objectives: Cell-culture studies reported that prokaryotic RNA molecules among the various microbe-associated molecular patterns (MAMPs) were uniquely present in live bacteria and were categorized as viability-associated MAMPs. They also reported that specific nucleotide modifications are instrumental in the discrimination between self and nonself RNAs. The aim of this study was to characterize the in vivo immune induction potential of prokaryotic and eukaryotic ribosomal RNAs (rRNAs) using zebrafish embryos as novel whole animal model system. Additionally, we aimed to test the possible role of rRNA modifications in immune recognition. Results: We used three immune markers to evaluate the induction potential of prokaryotic rRNA derived from Escherichia coli and eukaryotic rRNAs from chicken (nonself) and zebrafish (self). Lipopolysaccharide (LPS) of Pseudomonas aeruginosa served as a positive control. E. coli rRNA had an induction potential equivalent to that of LPS. The zebrafish innate immune system could discriminate between self and nonself rRNAs. Between the nonself rRNAs, E. coli rRNA was more immunogenic than chicken rRNA. The in vitro transcript of zebrafish 18S rRNA gene without the nucleotide modifications was not recognized by its own immune system. Our data suggested that prokaryotic rRNA is immunostimulatory in vivo and could be useful as an adjuvant.

    DOI: 10.1186/s13104-019-4878-8


  • Abnormal development of zebrafish after knockout and knockdown of ribosomal protein L10a Reviewed

    Palasin, K., Uechi, T., Yoshihama, M., Srisowanna, N., Choijookhuu, N., Hishikawa, Y., Kenmochi, N., Chotigeat, W.

    Scientific Reports   2019.12

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.1038/s41598-019-54544-w


  • Zebrafish models of Diamond-Blackfan anemia: A tool for understanding the disease pathogenesis and drug discovery Reviewed

    Uechi T, Kenmochi N

    Pharmaceuticals   2019.10

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    Language:English   Publishing type:Research paper (scientific journal)  

  • A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS Reviewed

    McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC, Ruggero D

    eLife   2019.9

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    Language:English   Publishing type:Research paper (scientific journal)  

    DOI: 10.7554/eLife.48847

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Books 【 display / non-display

  • The role of alternative mRNA splicing in heart development

    Bittel D.C., Kibiryeva N., Kenmochi N., Patil P., Uechi T., Rongish B., Filla M., Marshall J., Artman M., Johnson R., O’Brien J.E.( Role: Sole author)

    Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension  2020.1  ( ISBN:9789811511844

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    Research in the last 10 years has led to improved understanding of the genetic regulation of vertebrate heart development, but despite this effort, approximately 70% of all congenital heart defects (CHDs) still have an unknown etiology. Alternative splicing of mRNA has been documented to play roles in normal and abnormal development. Dysregulated splicing of mRNA has been shown to cause heart defects in mice, however a link between mRNA splicing and CHDs has not yet been shown in humans. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF) relative to the RV of normally developing infants. Moreover, there was a significant decrease in the level of 12 scaRNAs (small cajal body associated RNAs) in the RV from infants with TOF. These small noncoding RNAs guide the biochemical modification of specific nucleotides in spliceosomal RNAs that are critical for spliceosomal function. We used primary cells derived from the RV of infants with TOF to show a direct link between scaRNA levels and alteration in mRNA splicing of several genes that regulate heart development. We modified the expression of sets of scaRNAs and consequentially documented distinctive mRNA splicing, accompanied by corresponding protein isoform changes suggesting a unique contribution by each scaRNA. Furthermore, we knocked down two homologous scaRNAs in zebrafish and saw a disruption of heart development with an accompanying alteration in splice isoforms of cardiac regulatory genes. These combined results provide compelling evidence that scaRNAs contribute to the regulation of cardiac development by fine-tuning the fidelity of the spliceosome that adjusts exon retention as cell differentiation occurs. Importantly, our findings are consistent with the concept that disruption of mRNA splicing patterns during early embryonic development disturbs normal signaling pathways, resulting in conotruncal misalignment and TOF.

    DOI: 10.1007/978-981-15-1185-1_53


  • 大・中・小動物実験プロトコル

    宮崎大学動物実験プロトコール編集委員会( Role: Sole author)

    宮日文化情報センター  2016.3 

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    Language:Japanese Book type:Scholarly book

MISC 【 display / non-display

  • Development of a zebrafish model of congenital anemia and drug screening

    Kenmochi Naoya, Uechi Tamayo, Yoshihama Maki

    The Japanese Journal of Pediatric Hematology / Oncology   56 ( 5 )   402 - 406   2019

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution)   Publisher:The Japanese Society of Pediatric Hematology / Oncology  

    Diamond–Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by diminished numbers of erythroid progenitors. Although it is known that the ribosome is involved in the DBA onset, the molecular pathogenesis of this disease remains unknown and there are no clinically effective treatments available. We developed a zebrafish model of DBA and analyzed the pathogenic mechanism of this disease using this model. Zebrafish has many advantages in studying disease mechanisms, including the fast development and transparency of its embryos and its features conserved in humans. In addition, <i>in vivo</i> chemical screenings enable us to efficiently identify drug candidates. In this review, we introduce our approach to understand the pathogenic mechanism of DBA and to discover drug candidates using zebrafish as an animal model.

    DOI: 10.11412/jspho.56.402

  • リボソームタンパク質と翻訳制御

    上地珠代, 剣持直哉

    生体の科学:細胞の分子構造と機能-核以外の細胞小器官   63 ( 5 )   362 - 363   2012.10

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution)   Publisher:医学書院  


  • リボソーム病 : 翻訳装置のシステム障害

    上地 珠代, 剣持 直哉

    遺伝子医学mook   15   79 - 84   2009.11

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    Language:Japanese   Publishing type:Article, review, commentary, editorial, etc. (bulletin of university, research institution)   Publisher:メディカルドゥ  


Presentations 【 display / non-display

  • Depletion of ribosomal proteins and mRNA-specific translation control: studying the molecular pathogenesis of congenital anemia using zebrafish Invited


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    Event date: 2022.11.30 - 2022.12.2

    Language:Japanese   Presentation type:Oral presentation (invited, special)  

  • Exploring the molecular pathogenesis of ribosomopathies using zebrafish disease models


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    Event date: 2022.11.30 - 2022.12.2

    Presentation type:Oral presentation (general)  

  • リボソームの異常と疾患〜未知の翻訳機構の解明をめざす〜 Invited


    慶應義塾大学先端研究セミナー  2022.10.18 

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    Event date: 2022.10.18

    Language:Japanese   Presentation type:Public lecture, seminar, tutorial, course, or other speech  

  • 先天性貧血とリボソームの異常 〜ゼブラフィッシュを用いて未知の翻訳機構の解明をめざす〜 Invited


    第27回 八幡平造血セミナー  (オンライン)  中外製薬株式会社

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    Event date: 2021.8.21

    Language:Japanese   Presentation type:Oral presentation (invited, special)  


  • Loss of rRNA modifications alters the efficiency of tRNA accommodation Invited

    Tamayo Uechi, Mary McMahon, Davide Ruggero

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    Event date: 2019.12.3 - 2019.12.6

    Language:Japanese   Presentation type:Symposium, workshop panel (nominated)  

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Grant-in-Aid for Scientific Research 【 display / non-display

  • mRNA選択的な翻訳制御機構の解明 International coauthorship

    Grant number:16KK0185  2017.11 - 2020.03

    科学研究費補助金  国際共同研究加速基金(国際共同研究強化)

  • 自己免疫とRNA修飾:全身性エリテマトーデス発症の分子機構 研究課題

    Grant number:20200070  2008.04 - 2010.03

    科学研究費補助金  新学術領域研究(研究課題提案型)

  • 翻訳後修飾としてのチロシン硫酸化の空間および時間的制御機構の理解と機能解明

    Grant number:22H02262  2022.04 - 2026.03

    独立行政法人日本学術振興会  科学研究費補助金   基盤研究(B)

    榊原 陽一、

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  • 病態脳における小胞体プロテオスタシス破綻によるコレステロール合成不全と脳委縮

    Grant number:22H02954  2022.04 - 2025.03

    科学研究費補助金  基盤研究(B)

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  • 先天性貧血を引き起こすmRNA特異的な翻訳調節機構の解明 研究課題

    Grant number:22K08508  2022.04 - 2025.03

    独立行政法人日本学術振興会  科学研究費補助金   基盤研究(C)

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    Authorship:Principal investigator 

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