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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
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    References listed on IDEAS

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    1. 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.
    2. 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.
    3. 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.
    4. 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.
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