RNA interference (RNAi) inhibits growth of Plasmodium falciparum.

Abstract

RNA interference (RNAi) causes degradation of targeted endogenous RNA in many diverse organisms. Erythrocyte-infecting stages of the malaria parasite Plasmodium falciparum were treated with double-stranded RNA (dsRNA) encoding a segment of the gene encoding dihydroorotate dehydrogenase (DHODH). DHODH is an enzyme in pyrimidine biosynthesis, essential for parasite growth. A decrease in parasite growth (P<0.0005) correlated with a decrease in levels of DHODH mRNA. Control treatments with single-stranded RNA, dsRNA encoding the circumsporozoite protein (a stage-specific protein not expressed in the asexual blood stage) and dsRNA encoding a gene from the related organism Toxoplasma gondii did not inhibit growth. As a test for the RNAi assay, parasites were treated with dsRNA encoding chorismate synthase (CS), an enzyme thought to be involved in folate synthesis, to examine the requirement for this enzyme for parasite growth. Growth decreased (P<0.001) though less markedly than by dsRNA encoding DHODH. These results demonstrate the utility of this assay in assessing requirements for gene products, and their potential as chemotherapeutic targets.

• Authors: Louisa McRobert, Glenn A McConkey
• Journal: Molecular and biochemical parasitology (Mol Biochem Parasitol) Vol. 119 Issue 2 Pg. 273-8 (Feb 2002) ISSN: 0166-6851 [Print] Netherlands
• PMID: 11814579 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Pyrimidines
• RNA, Double-Stranded
• RNA, Messenger
• Oxidoreductases
• dehydroorotate dehydrogenase
• chorismate synthase
• Phosphorus-Oxygen Lyases
• Chorismic Acid

Topics

• Animals
• Chorismic Acid (metabolism)
• Oxidoreductases (biosynthesis, genetics, metabolism)
• Phosphorus-Oxygen Lyases (genetics, metabolism)
• Plasmodium falciparum (enzymology, genetics, growth & development)
• Pyrimidines (biosynthesis)
• RNA, Double-Stranded (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)