George Jerrin Thomas, Burman Nathaniel, Wilkinson Royce A, de Silva Senuri, McKelvey-Pham Quynh, Buyukyoruk Murat, Dale Adelaide, Landman Hannah, Graham Ava B, DeLuca Steven Z, Wiedenheft Blake
Montana State University, Bozeman, Department of Microbiology and Cell Biology, Bozeman, MT, USA.
Nat Commun. 2025 Sep 26;16(1):8459. doi: 10.1038/s41467-025-63285-6.
Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses and retrotransposons. However, recent evidence suggests that RTs have been conscripted by cells for diverse roles in antiviral defence. Here we determine structures of a type I-A retron, which explain how RNA, DNA, RT, HNH-nuclease and four molecules of a structure maintenance of chromosome (SMC)-family ATPase assemble into a 364 kDa complex that provides phage defence. We show that phage-encoded nucleases trigger degradation of the retron-associated DNA, leading to activation of the HNH nuclease. The HNH nuclease cleaves tRNA, stalling protein synthesis and arresting viral replication. Taken together, these data reveal diverse and paradoxical roles for RTs in the perpetuation and elimination of genetic parasites.
逆转录酶（RTs）在逆转录病毒和逆转座子的复制与传播中具有既定作用。然而，最近的证据表明，细胞已征用RTs在抗病毒防御中发挥多种作用。在此，我们确定了I-A型反转录子的结构，这些结构解释了RNA、DNA、RT、HNH核酸酶和四个染色体结构维持（SMC）家族ATP酶分子如何组装成一个提供噬菌体防御的364 kDa复合物。我们表明，噬菌体编码的核酸酶触发与反转录子相关的DNA降解，导致HNH核酸酶激活。HNH核酸酶切割tRNA，使蛋白质合成停滞并阻止病毒复制。综上所述，这些数据揭示了RTs在遗传寄生物的延续和消除中具有多种矛盾的作用。
