Identification of specific inhibitors for a trypanosomatid RNA editing reaction

Shuang Liang, Gregory J. Connell

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 IC50 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. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)2435-2441
Number of pages7
JournalRNA
Volume16
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • D-sphingosine
  • Inhibitors
  • Protoporphyrin IX
  • RNA editing
  • Suramin
  • Trypanosomatid

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