generate double-strand breaks (DSBs) in specifically impairs the interferon response. Nandhitha Uma Naresh and Cole M. Haynes mtDNA. They used RNA sequencing to analyse The study highlights an immunostimu- are in the Department of Molecular, Cell and changes in gene expression in cells treated latory role for mtRNA. However, questions Cancer Biology, University of Massachusetts with mTLNs, and found increased transcrip- remain. For instance, mtRNA molecules are Medical School, Worcester, Massachusetts tion of nuclear genes involved in the innate highly unstable in nature11 — how are mtRNAs 01605, USA. immune response; these included inter- stabilized so that they accumulate in the cyto- e-mail:
[email protected] feron-response genes, which are typically sol, as was observed in the current study? involved in combating viral infections. The Another avenue for further investigation is 1. Shpilka, T. & Haynes, C. M. Nature Rev. Mol. Cell Biol. 19, authors also found that the transcription the factors that stimulate the formation of 109–120 (2018). factor STAT1 was modified by phosphate BAK–BAX pores following mtDNA breaks. It 2. Guo, X. et al. Nature 579, 427–432 (2020). groups and relocated to the nucleus — a key would be of broad interest to study whether 3. Tigano, M., Vargas, D. C., Tremblay-Belzile, S., Fu, Y. & 8 Sfeir, A. Nature 591, 477–481 (2021). part of the interferon response . drugs that inhibit this pore formation can 4. McArthur, K. et al. Science 359, eaao6047 (2018). Breaks in mtDNA that occur through suppress an inflammatory immune response. 5. White, M. J. et al. Cell 159, 1549–1562 (2014).