Nat Immunol. 2012 Sep 18;13(10):946. doi: 10.1038/ni.2439.
MicroRNA-based resistance to malaria.
Erythrocytes heterozygous (HbSA) or homozygous (HbSS) for the gene linked to sickle cell anemia have well-documented resistance to infection by the malaria parasite Plasmodium falciparum. In Cell Host & Microbe, Chi and colleagues describe a radical, previously unknown mechanism of sickle cell–dependent resistance to P. falciparum. Although they lack a nucleus, erythrocytes are replete with microRNA. The authors find that HbSA erythrocytes and, even more notably, HbSS erythrocytes are especially enriched for four microRNAs (Let7i, miR181, miR223 and miR451) and that these are actively translocated to the parasite. Through the use of transfection and antagomirs, the authors demonstrate that miR451 is especially important in controlling parasitemia. As orthologous microRNA-processing machinery is absent from P. falciparum, miR451 seems to abrogate parasite translation by a previously unknown mechanism. This microRNA covalently binds to a specific parasite mRNA (PKA-R) to form a single contiguous mRNA molecule that is poorly translated. As PKA-R is important for P. falciparumgrowth, this represents a potentially important endogenous mechanism of regulating parasite growth.
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