De novo gene synthesis by an antiviral reverse transcriptase

• 成果类型: Article
• 署名作者: Tang, Stephen; Conte, Valentin; Zhang, Dennis J.; Zedaveinyte, Rimante; Lampe, George D.; Wiegand, Tanner; Tang, Lauren C.; Wang, Megan; Walker, Matt W. G.; George, Jerrin Thomas; Berchowitz, Luke E.; Jovanovic, Marko; Sternberg, Samuel H.
• 署名单位: Columbia University; Columbia University; Columbia University; Montana State University System; Montana State University Bozeman; Columbia University; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12835
• DOI: 10.1126/science.adq0876
• 发表日期: 2024-10-04
• 关键词: ribosome rescue; protein; alignment; mechanisms; prediction; immunity; ELEMENTS; repeats; program

摘要

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. We show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis through rolling circle reverse transcription of a noncoding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. This DNA product constitutes a protein-coding, nearly endless open reading frame (neo) gene whose expression leads to potent cell growth arrest, 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.