Study Identifies Two Proteins Key to Malaria Parasite’s Survival

A new study led by infectious disease experts at University of California-Riverside (UCR) has identified two proteins that are vital to survival of Plasmodium falciparum, the parasite responsible for malaria. The findings could help prevent the spread of the mosquito-borne disease, which killed more than half a million people in 2020.

Using advanced genome editing technology, the team was able to show that RAP01 and RAP21 were “intimately linked” to the mitochondria of P. falciparum. “Without these proteins, the mitochondria cannot ensure the parasite’s function and it dies,” says Karine Le Roch, a professor of molecular, cell and systems biology and director of the UCR Center for Infectious Disease and Vector Research.  “Understanding the exact function of this pair of proteins could lead to the discovery of new therapeutic strategies to fight malaria.” 

According to Le Roch, RAP01 and RAP21 were detected and expressed at higher levels at every stage of the Apicomplexan parasite lifecycle. When her team used the CRISPR-Cas9 genome-editing tool to knock down these proteins, which was followed by death of the parasite followed.

The pair of proteins belong to the “RNA-binding domain abundant in Apicomplexans,” or RAP, protein family that has been identified in several organisms but remains poorly characterized. Le Roch says human cells have only a small number of the proteins, but Apicomplexan parasites such as P. falciparum have many. This may be because the mitochondria in Apicomplexan parasites have many fragmented ribosomal RNAs in their mitochondria.

“RAP01 and RAP21 may be instrumental in bringing all the fragmented ribosomal RNAs together,” said Le Roch. “These RNAs are essential for protein translation in the mitochondria. If drugs can be developed to knock down RAP01 and RAP21, the whole process would be interrupted, leading to the parasite’s death. Such drugs are unlikely to affect human mitochondria because they differ vastly from mitochondria of Apicomplexan parasites.”

The findings were reported in a recent issue of Nature Communications.