Sensing Non-Self DNA

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Science  30 Oct 2009:
Vol. 326, Issue 5953, pp. 645
DOI: 10.1126/science.326_645c

One way the immune system recognizes infection is by sensing the presence of foreign nucleic acids in the cytoplasm. Although it had been established that microbial double-stranded DNA (dsDNA) triggered the production of the inflammatory cytokine interferon-β, the identity of the dsDNA sensor remained elusive.

Chiu et al. and Ablasser et al. suggest that RNA polymerase III (Pol III) is the culprit. Pol III, which transcribes genes encoding several kinds of RNA (such as transfer and ribosomal), has been shown to be present in the cytoplasm, but what it did there was unclear. These authors show that cytoplasmic Pol III transcribes AT-rich microbial dsDNA into 5′-triphosphate–containing RNA that is then detected by the retinoic acid–induced gene I (RIG-I), which proceeds to switch on the production of interferon-β. In the absence of Pol III, infection with Legionella pneumophila or Epstein-Barr virus does not induce interferon-β, indicating that Pol III is required for proper immunity both to bacterial and to viral infection.

Cell 138, 576 (2009); Nat. Immunol. 10, 1065 (2009).

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