Molecular Parasitology , RNA Modification and Repair

分子寄生虫学

Department of Infection Biology, Faculty of Medicine

Ho Lab: Welcome
 
 

Gene Expression in Parasitic Protozoan

Parasitic protozoa are causative agents of widespread human diseases, including malaria (caused by Plasmodium falciparum), African sleeping sickness (Trypanosome brucei), and Chagas' disease (Trypanosome cruzi). Because these parasites diverged early from the main branch of the eukaryotic lineage, their unusual mechanisms of gene expression reflect ancient eukaryotic functions that have been preserved to present. By studying the process of gene expression, not only may we learn about the evolution of higher eukaryotes, but we can also identify parasite specific processes that can be exploited as targets for novel therapeutic intervention. (Read More ...)

Selected Publications

  1. Ho CK and Shuman S. (1999) Distinct Roles for CTD Ser2 and Ser5 Phosphorylation in the Recruitment and Allosteric Activation of Mammalian mRNA Capping Enzyme. Molecular Cell 3: 405-411.

  2. Ho CK and Shuman S. (2001) A Yeast-like mRNA Capping Apparatus in Plasmodium falciparum.Proc. Natl. Acad. Sci. USA 98: 3050-3055

  3. Changela A, Ho CK, Martins A, Shuman S, and Mondragon A. (2001) Structure and Mechanism of the RNA Triphosphatase Component of Mammalian mRNA Capping Enzyme. EMBO J 20: 2575-2586.

  4. Ho CK and Shuman S. (2002) Bacteriophage T4 RNA Ligase 2 (gp 24.1) Exemplifies a Family of RNA Ligases Found in All Phylogenic Domains. Proc. Natl. Acad. Sci. USA 99: 12709-12714.

  5. Chiu YL, Ho CK, Saha N, Schwer B, Shuman S, and Rana TM. (2002) Tat Stimulates Cotranscriptional Capping of HIV-1 mRNA. Molecular Cell 10: 585-597.

  6. Ho CK, Wang LK, Lima CD and Shuman S. (2004) Structure and Mechanism of RNA Ligase. Structure 12: 327-339.

  7. Pfeffer S, Sewer A, Lagos-Quintana M, Sheridan R, Sander C, Grässer FA, van Dyk LF, Shuman S, Ho CK, Chien M, Russo JJ, Ju J, Randall G, Lindenbach BD, Rice CM, Simon V, Ho DD, Zavolan M, and Tuschl T. (2005) Identification of the MicroRNAs of the Herpesvirus Family. Nature Method 2: 269-276.

  8. Takagi Y, Sindkar S, Ekonomidis D, Hall MP and Ho CK. (2007) Trypanosoma brucei Encodes a Bifunctional Capping Enzyme Essential for Cap 4 Formation on the Spliced Leader RNA. J. Biol. Chem. 282: 15995-16005.

  9. Torchea C, Takagi Y and Ho CK. (2008) Archaea RNA Ligase is a Homodimeric Protein that Catalyzes Intramolecular Ligation of Single-Stranded RNA and DNA. Nucleic Acid Res. 36: 6218 - 6227.

  10. Ignatochkina AV, Takagi Y, Liu Y, Nagata K, and Ho CK. (2015) The messenger RNA decapping and recapping pathway in Trypanosoma. Proc. Natl. Acad. Sci. USA 112: 6955-5960.

  11. Smith P, Ho CK, Takagi Y, Djaballah H, and Shuman S. (2016) Nanomolar Inhibitors of Trypanosoma brucei RNA Triphosphatase. mBIO 7: e00058-16

  12. Gu H, Yoshinari S, Ghosh R,Ignatochkina AV, Gollnick PD, Murakami KS and Ho CK. (2016) Structural and Mutational Analysis of Archaeal ATP-dependent RNA ligase Identifies Amino Acid Required for RNA Binding and Catalysis. Nucleic Acid Res. 44: 2337-2347

  13. Ho CK. (2017)  Detection and Identification of Uncapped RNA by Ligation-Mediated Reverse Transcription Polymerase Chain Reaction . mRNA Processing - Methods in Molecular Biology, 1948: 1-9

  14. Yoshinari S, Liu Y, Gollnick PG and Ho CK. (2017) Cleavage of 3’-terminal adenosine by archaeal ATP-dependent RNA ligase. Sci. Rep. 7:11662.

本研究室では、マラリア、アフリア睡眠病などを引き起こす寄生虫の遺伝子発現メカニズムを研究してます。特に転写中に起きるmRNAキャッピングは寄生虫とヒトとでは異なってるため、これを標的とした新薬の開発を目指しています。 キャッピングの活性を生化学的に解析し、RNAi法によりそれぞれのキャップ酵素の役割を解析しています。


RNA Modification and Repair

Living cells are under constant attack by various environmental and cellular agents that induce breakage of both DNA and RNA. If not repaired, this type of genomic damage can lead to changes in gene expression, mutation, or even cell death. While elaborate DNA repair pathways are understood in reasonable detail, our knowledge of how damage to RNA molecules is recognized and repaired remains very limited. One of the few facts that have been established is that RNA ligase - an enzyme that recognizes breaks in an RNA chain and joins the two ends together - is a key component of this repair process. (Read More ...)


その他にRNAの修復メカニズムを解明の研究を行っています。本研究室ではRNAを繋げる重要な酵素、RNAライゲーズの構造を明らかにし、RNAライゲーズがどのように損傷を受けたRNAを認識し修復するメカニズムを調べています。遺伝学的にはライゲーズが細胞の中でどのようなRNAを修復さしているかを検討しています。



Contents

  1. -Research Topics

  2. -Profile

  3. -Lab Members

  4. -Publications

  5. -Map / Access


  1. -研究テーマ

  2. -略歴

  3. -論文

  4. -アクセス


Faculty of Medicine

University of Tsukuba

1-1-1 Tennou-dai

Tsukuba, Ibaraki

JAPAN  305-8575


305-8575

茨城県 つくば市天王台1-1-1

筑波大学大学院 医学医療系


Phone

+81 29 853 5612 (direct)

029 853 5612 (直通)

 

Announcement

  1. Truong Tat Dang received an Outstanding Speaker Award at 16th International Joint Mini-Symposium between KU-NTU-UT (2017).

  2. Anna Ignatochkina received an Outstanding Speaker Award at 14th International Joint Mini-Symposium on Molecular and Cell Biology between KU-NTU-UT (2015).

  3. Jesavel Iguchi Aguisanda received a Best Presentation Award at Tsukuba Global Science Week 2015.