Albert Einstein College of Medicine, New York City
A biologist considers a link between jumping genes and immune-system enzymes.
Many viruses present a fierce threat to the body. They contain nucleic acids that, when free to roam in a cell’s cytoplasm, elicit an immune response involving proteins called interferons. Pairings of the nucleic-acid residues cytosine and guanine are especially good at this, unless they carry a chemical modification in the form of a methyl group. This modification is the norm for ‘jumping genes’, or retrotransposons, which can move around the human genome and were probably once viral genes themselves.
A team led by Daniel Stetson at the University of Washington in Seattle has uncovered a useful twist to this tale. While searching for proteins that interact with cytoplasmic nucleic acids, the researchers came across Trex1. Mutated versions of Trex1 are known to cause chilblain lupus in humans, and in mice lead to autoimmune myocarditis, whereby the immune system attacks the heart. Stetson et al. say that mice lacking Trex1 have huge numbers of retrotransposons in their heart muscles.
Critically, the authors’ molecular surveys reveal that Trex1 suppresses the rate at which jumping genes move around. This indicates that Trex1 protects the body from misidentifying its own parts as ‘foreign’ by degrading retrotransposons and thus preventing them from overloading the system (D. B. Stetson et al. Cell 134, 587–598; 2008).
That jumping genes have the potential to overwhelm the system in this way was unexpected. Most experts had assumed that the addition of methyl groups took care of quenching them. But if retrotransposons are made at a rate that triggers inflammation, as Stetson and his colleagues’ experiments propose, it could open up a whole new avenue for research. Everyone studying lupus and related diseases should be excited.