美国麻省理工学院张峰团队的研究发现,由噬菌体触发的反转录可利用非编码RNA生成有毒的重复基因。该研究于2024年8月29日发表于国际学术期刊《科学》杂志。
研究人员发现在DRT2防御系统中,反转录酶与邻近的假结非编码RNA结合。噬菌体感染后,该RNA的模板区域被逆转录为串联重复序列,该序列重塑了启动子和开放阅读框,导致毒性重复蛋白表达和终止感染反应。
这种活性的生化重组和冷冻电镜为重复序列的合成提供了分子基础。该研究表明非编码RNA来源的合成基因是原核生物基因调控的一种新模式。
据悉,逆转录经常用于实现细胞功能,在原核生物中,逆转录与保护细胞免受病毒感染有关,但其防御的基本机制尚不清楚。
附:英文原文
Title: Phage-triggered reverse transcription assembles a toxic repetitive gene from a noncoding RNA
Author: Max E. Wilkinson, David Li, Alex Gao, Rhiannon K. Macrae, Feng Zhang
Issue&Volume: 2024-08-29
Abstract: Reverse transcription has frequently been co-opted for cellular functions and in prokaryotes is associated with protection against viral infection, but the underlying mechanisms of defense are generally unknown. Here, we show that in the DRT2 defense system the reverse transcriptase binds a neighboring pseudoknotted noncoding RNA. Upon bacteriophage infection, a template region of this RNA is reverse transcribed into an array of tandem repeats that reconstitute a promoter and open reading frame, allowing expression of a toxic repetitive protein and an abortive infection response. Biochemical reconstitution of this activity and cryogenic electron microscopy provide a molecular basis for repeat synthesis. Gene synthesis from a noncoding RNA is a new mode of genetic regulation in prokaryotes.
DOI: adq3977
Source: https://www.science.org/doi/10.1126/science.adq3977