Deadliest Malaria Parasite Uses Anti-Sense Long Noncoding RNAs (lncRNAs) to Specifically Regulate and Periodically Switch Expression of Single Members of Its ~50-var-Gene-Family to Avoid Detection by Human Immune System

Up to one million people, mainly pregnant woman and young children, are killed each year by the Plasmodium falciparum parasite, which causes the most devastating form of human malaria. Now, researchers at the Hebrew University of Jerusalem have revealed the genetic trickery this deadly parasite deploys to escape attack by the human immune system. The parasite is known to replicate within the circulating blood of infected individuals and modify the surface of infected red blood cells. Its virulence comes from its impressive ability to hide from the immune system by selectively changing which surface proteins it displays. This sophisticated game of hide-and-seek, which involves continually alternating the foreign molecules, called antigens, that can trigger an immune response, is called antigenic variation. Previous research has shown that the antigens the parasite selectively expresses, and which are displayed at the surfaces of infected red blood cells, are encoded by members of a gene family named var. The multi-gene var family codes for approximately 50 variant adhesive proteins expressed in a mutually exclusive manner at the surface of infected red blood cells. The parasite tightly regulates the expression of these var genes so that only one is expressed at any given time, while the rest of the family is maintained as silent. Understanding this complex mechanism is essential to understanding how the deadly Plasmodium falciparum parasite evades the human immune system. It is also more broadly important to science because the process by which cells can express a single gene while keeping alternative genes silent is one of the unsolved mysteries in the field of eukaryotic gene expression.
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