Translocation of sickle cell erythrocyte microRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance.

Published

Journal Article

Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.

Full Text

Duke Authors

Cited Authors

  • LaMonte, G; Philip, N; Reardon, J; Lacsina, JR; Majoros, W; Chapman, L; Thornburg, CD; Telen, MJ; Ohler, U; Nicchitta, CV; Haystead, T; Chi, J-T

Published Date

  • August 16, 2012

Published In

Volume / Issue

  • 12 / 2

Start / End Page

  • 187 - 199

PubMed ID

  • 22901539

Pubmed Central ID

  • 22901539

Electronic International Standard Serial Number (EISSN)

  • 1934-6069

Digital Object Identifier (DOI)

  • 10.1016/j.chom.2012.06.007

Language

  • eng

Conference Location

  • United States