研究人员发现,防御相关逆转录酶(DRT)系统编码了一种前所未有的免疫途径,该途径涉及通过滚环逆转录从头基因合成。这一过程中,编程模板跳跃在非编码RNA(ncRNA)上生成了一个串联的cDNA,并在病毒感染后形成双链DNA。
值得注意的是,这一DNA产物构成了一个具有蛋白编码功能、几乎无限的ORF(neo)基因,其表达导致强效的细胞生长停滞,从而限制了病毒感染。该研究突显了通过RNA模板创建基因来优雅地扩展基因组编码潜力,并挑战了沿着基因组DNA一维轴编码遗传信息的传统范式。
据了解,DRT系统通过DNA合成保护细菌免受病毒感染,但其DNA产物的身份和功能仍然不甚清楚。
附:英文原文
Title: De novo gene synthesis by an antiviral reverse transcriptase
Author: Stephen Tang, Valentin Conte, Dennis J. Zhang, Rimant edaveinyt, George D. Lampe, Tanner Wiegand, Lauren C. Tang, Megan Wang, Matt W. G. Walker, Jerrin Thomas George, Luke E. Berchowitz, Marko Jovanovic, Samuel H. Sternberg
Issue&Volume: 2024-08-08
Abstract: 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.
DOI: adq0876
Source: https://www.science.org/doi/10.1126/science.adq0876