RNA interference of a trypanosome topoisomerase II causes progressive loss of mitochondrial DNA

Z. Wang, P. T. Englund

Research output: Contribution to journalArticle

Abstract

We studied the function of a Trypanosoma brucei topoisomerase II using RNA interference (RNAi). Expression of a topoisomerase II double-stranded RNA as a stem-loop caused specific degradation of mRNA followed by loss of protein. After 6 days of RNAi, the parasites' growth rate declined and the cells subsequently died. The most striking phenotype upon induction of RNAi was the loss of kinetoplast DNA (kDNA), the cell's catenated mitochondrial DNA network. The loss of kDNA was preceded by gradual shrinkage of the network and accumulation of gapped free minicircle replication intermediates. These facts, together with the localization of the enzyme in two antipodal sites flanking the kDNA, show that a function of this topoisomerase II is to attach free minicircles to the network periphery following their replication.

Original languageEnglish (US)
Pages (from-to)4674-4683
Number of pages10
JournalThe EMBO journal
Volume20
Issue number17
DOIs
StatePublished - Sep 3 2001

Fingerprint

Kinetoplast DNA
Type II DNA Topoisomerase
Trypanosomiasis
RNA Interference
Mitochondrial DNA
RNA
Catenated DNA
Trypanosoma brucei brucei
Double-Stranded RNA
RNA Stability
Parasites
Phenotype
Degradation
Messenger RNA
Enzymes
Growth
Proteins

Keywords

  • Kinetoplast DNA
  • Minicircle
  • RNAi
  • Topoisomerase II

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

RNA interference of a trypanosome topoisomerase II causes progressive loss of mitochondrial DNA. / Wang, Z.; Englund, P. T.

In: The EMBO journal, Vol. 20, No. 17, 03.09.2001, p. 4674-4683.

Research output: Contribution to journalArticle

Wang, Z. ; Englund, P. T. / RNA interference of a trypanosome topoisomerase II causes progressive loss of mitochondrial DNA. In: The EMBO journal. 2001 ; Vol. 20, No. 17. pp. 4674-4683.
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