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<p>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<sub>Ser</sub>, 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.</p>

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Structural basis of antiphage defence by an ATPase-associated reverse transcriptase

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Jerrin Thomas George,
  • Nathaniel Burman,
  • Royce A. Wilkinson,
  • Senuri de Silva,
  • Quynh McKelvey-Pham,
  • Murat Buyukyoruk,
  • Adelaide Dale,
  • Hannah Landman,
  • Ava B. Graham,
  • Steven Z. DeLuca,
  • Blake Wiedenheft

摘要

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 tRNASer, 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.