People who dread flying have, in recent years, been given yet more fodder for their fear. Individuals who remain seated without moving during long flights can develop dangerous blood clots. Susceptibility to the condition that can lead to so-called economy-class syndrome and other clotting-related problems¿a disorder known as thrombophilia¿has a known genetic risk factor: a mutation in the gene that codes for the coagulation factor prothrombin. Yet exactly how this mutation, which occurs in 1 to 2 percent of the population, causes thrombophilia has eluded scientists. Oddly, the mutation raises prothrombin levels in the blood but does not alter the composition of the prothrombin protein. Now new research published in the current issue of Nature Genetics finally reveals the mysterious mechanism.

Andreas Kulozik of Humboldt University in Berlin and his colleagues found that the mutation influences the production of prothrombin RNA, which directs synthesis of the protein. Prothrombin RNA production normally proceeds such that the prothrombin RNA precursor molecule is cleaved at one end, releasing the mature prothrombin RNA. The mutation, it turns out, renders this cleavage site extra-sensitive, thus spurring the production rate of mature prothrombin RNA, which in turn yields more of the coagulation factor itself. This enhanced processing efficiency, the authors note, "represents a remarkable example of how a quantitatively minor activation of RNA processing can predispose to a common and serious disease."

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