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De novo gene synthesis by an antiviral reverse transcriptase
Science ( IF 44.7 ) Pub Date : 2024-08-08 , DOI: 10.1126/science.adq0876
Stephen Tang 1 , Valentin Conte 1 , Dennis J Zhang 2 , Rimantė Žedaveinytė 1 , George D Lampe 1 , Tanner Wiegand 1 , Lauren C Tang 2 , Megan Wang 1 , Matt W G Walker 2 , Jerrin Thomas George 1 , Luke E Berchowitz 3, 4 , Marko Jovanovic 2 , Samuel H Sternberg 1
Affiliation  

Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their DNA products remain largely unknown. Here we show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis via rolling circle reverse transcription of a non-coding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. Remarkably, this DNA product constitutes a protein-coding, nearly endless ORF ( neo ) gene whose expression leads to potent cell growth arrest, thereby restricting the viral infection. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation, and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.

中文翻译:


通过抗病毒逆转录酶从头合成基因



防御相关逆转录酶 (DRT) 系统进行 DNA 合成以保护细菌免受病毒感染,但其 DNA 产物的身份和功能仍然很大程度上未知。在这里,我们展示了 DRT2 系统编码了一种前所未有的免疫途径,该途径涉及通过非编码 RNA (ncRNA) 的滚环逆转录从头合成基因。在 ncRNA 上跳跃的编程模板会生成串联 cDNA,该 cDNA 在病毒感染后变成双链。值得注意的是,这种 DNA 产物构成了一种蛋白质编码的、几乎无限的 ORF (neo) 基因,其表达导致有效的细胞生长停滞,从而限制病毒感染。我们的工作强调了通过 RNA 模板基因创建来优雅地扩展基因组编码潜力,并挑战沿基因组 DNA 一维轴编码的遗传信息的传统范例。
更新日期:2024-08-08
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