IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33109-y.html
   My bibliography  Save this article

Genome-scale RNA interference profiling of Trypanosoma brucei cell cycle progression defects

Author

Listed:
  • Catarina A. Marques

    (University of Dundee
    University of Glasgow)

  • Melanie Ridgway

    (University of Dundee)

  • Michele Tinti

    (University of Dundee)

  • Andrew Cassidy

    (Ninewells Hospital and School of Medicine)

  • David Horn

    (University of Dundee)

Abstract

Trypanosomatids, which include major pathogens of humans and livestock, are flagellated protozoa for which cell cycle controls and the underlying mechanisms are not completely understood. Here, we describe a genome-wide RNA-interference library screen for cell cycle defects in Trypanosoma brucei. We induced massive parallel knockdown, sorted the perturbed population using high-throughput flow cytometry, deep-sequenced RNAi-targets from each stage and digitally reconstructed cell cycle profiles at a genomic scale; also enabling data visualisation using an online tool ( https://tryp-cycle.pages.dev/ ). Analysis of several hundred genes that impact cell cycle progression reveals >100 flagellar component knockdowns linked to genome endoreduplication, evidence for metabolic control of the G1-S transition, surface antigen regulatory mRNA-binding protein knockdowns linked to G2M accumulation, and a putative nucleoredoxin required for both mitochondrial genome segregation and for mitosis. The outputs provide comprehensive functional genomic evidence for the known and novel machineries, pathways and regulators that coordinate trypanosome cell cycle progression.

Suggested Citation

  • Catarina A. Marques & Melanie Ridgway & Michele Tinti & Andrew Cassidy & David Horn, 2022. "Genome-scale RNA interference profiling of Trypanosoma brucei cell cycle progression defects," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33109-y
    DOI: 10.1038/s41467-022-33109-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33109-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33109-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Charles Coutton & Alexandra S. Vargas & Amir Amiri-Yekta & Zine-Eddine Kherraf & Selima Fourati Mustapha & Pauline Tanno & Clémentine Wambergue-Legrand & Thomas Karaouzène & Guillaume Martinez & Serge, 2018. "Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human," Nature Communications, Nature, vol. 9(1), pages 1-18, December.
    2. Shilpi Khare & Advait S. Nagle & Agnes Biggart & Yin H. Lai & Fang Liang & Lauren C. Davis & S. Whitney Barnes & Casey J. N. Mathison & Elmarie Myburgh & Mu-Yun Gao & J. Robert Gillespie & Xianzhong L, 2016. "Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness," Nature, Nature, vol. 537(7619), pages 229-233, September.
    3. Ying Wei & Huiqing Hu & Zhao-Rong Lun & Ziyin Li, 2014. "Centrin3 in trypanosomes maintains the stability of a flagellar inner-arm dynein for cell motility," Nature Communications, Nature, vol. 5(1), pages 1-11, September.
    4. Richard Broadhead & Helen R. Dawe & Helen Farr & Samantha Griffiths & Sarah R. Hart & Neil Portman & Michael K. Shaw & Michael L. Ginger & Simon J. Gaskell & Paul G. McKean & Keith Gull, 2006. "Flagellar motility is required for the viability of the bloodstream trypanosome," Nature, Nature, vol. 440(7081), pages 224-227, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jan Silhan & Pavla Fajtova & Jitka Bartosova & Brianna M. Hurysz & Jehad Almaliti & Yukiko Miyamoto & Lars Eckmann & William H. Gerwick & Anthony J. O’Donoghue & Evzen Boura, 2024. "Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Archie A. Khan & Harry C. Langston & Louis Walsh & Rebecca Roscoe & Shiromani Jayawardhana & Amanda Fortes Francisco & Martin C. Taylor & Conor J. McCann & John M. Kelly & Michael D. Lewis, 2024. "Enteric nervous system regeneration and functional cure of experimental digestive Chagas disease with trypanocidal chemotherapy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Xuanyan Jia & Leishu Lin & Siqi Guo & Lulu Zhou & Gaowei Jin & Jiayuan Dong & Jinman Xiao & Xingqiao Xie & Yiming Li & Sicong He & Zhiyi Wei & Cong Yu, 2024. "CLASP-mediated competitive binding in protein condensates directs microtubule growth," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Hao-Chi Hsu & Daqiang Li & Wenhu Zhan & Jianxiang Ye & Yi Jing Liu & Annie Leung & Junling Qin & Benigno Crespo & Francisco-Javier Gamo & Hao Zhang & Liwang Cui & Alison Roth & Laura A. Kirkman & Huil, 2023. "Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Michelle M. Shimogawa & Angeline S. Wijono & Hui Wang & Jiayan Zhang & Jihui Sha & Natasha Szombathy & Sabeeca Vadakkan & Paula Pelayo & Keya Jonnalagadda & James Wohlschlegel & Z. Hong Zhou & Kent L., 2023. "FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33109-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.