ArticleRNA (New York, N.Y.)2010
Identification of specific inhibitors for a trypanosomatid RNA editing reaction.
Article in RNA (New York, N.Y.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Pilot-Scale Screening of Clinically Approved Drugs to Identify Uridine Insertion/Deletion RNA Editing Inhibitors inACS infectious diseases · 2024Article
- Targeting RNA Structure to Inhibit Editing in Trypanosomes.International journal of molecular sciences · 2023Article
- Hammerhead ribozyme-based U-insertion and deletion RNA editing assays for multiplexing in HTS applications.RNA (New York, N.Y.) · 2023Article
- Analyzing editosome function in high-throughput.Nucleic acids research · 2020Article
- A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs AgainstBioinformatics and biology insights · 2017Article
- A novel high-throughput activity assay for the Trypanosoma brucei editosome enzyme REL1 and other RNA ligases.Nucleic acids research · 2016Article
- Charge reduction and thermodynamic stabilization of substrate RNAs inhibit RNA editing.PloS one · 2015Article
- The double-edged sword in pathogenic trypanosomatids: the pivotal role of mitochondria in oxidative stress and bioenergetics.BioMed research international · 2014Review
- Inhibitors of RNA editing as potential chemotherapeutics against trypanosomatid pathogens.International journal for parasitology. Drugs and drug resistance · 2012Review
- Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays.Nucleic acids research · 2012Article
- The crystal structure of an oligo(U):pre-mRNA duplex from a trypanosome RNA editing substrate.RNA (New York, N.Y.) · 2011Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several mitochondrial mRNAs of the trypanosomatid protozoa are edited through the post-transcriptional insertion and deletion of uridylates. The reaction has provided insights into basic cellular biology and is also important as a potential therapeutic target for the diseases caused by trypanosomatid pathogens. Despite this importance, the field has been hindered by the lack of specific inhibitors that could be used as probes of the reaction mechanism or developed into novel therapeutics. In this study, an electrochemiluminescent aptamer-switch was utilized in a high-throughput screen for inhibitors of a trypanosomatid RNA editing reaction. The screen identified GW5074, mitoxantrone, NF 023, protoporphyrin IX, and D-sphingosine as inhibitors of insertion editing, with IC(50) values ranging from 1 to 3 μM. GW5074 and protoporphyrin IX are demonstrated to inhibit at or before the endonuclease cleavage that initiates editing and will be valuable biochemical probes for the early events of the in vitro reaction. Since protoporphyrin IX and sphingosine are both naturally present within the trypanosomatids, their effectiveness as in vitro inhibitors is also suggestive of the potential for in vivo modulatory roles.
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