近日，英国MRC分子生物学实验室
研究组展示了人类LINE-1 TPRT复合物的低温电镜结构，揭示了ORF2p的构象动力学及其对TPRT起始目标DNA的广泛重塑。研究人员观察到DNA第二链在第一链的反转录过程中有切口。结构预测确定了ORF2p上LINE-1相关因子（即PCNA和PABPC1）的高可信度结合位点。结合它们的结构数据，这表明了这些因子调节逆转录转位的机制，并提出了一个解释细胞中观察到的逆转录转位结果的TPRT模型。
据介绍，长穿插元件-1（LINE-1）逆转录转座子是人类中唯一活跃的自主转座子元件。它们通过靶引逆转录（target-引逆转录，TPRT）过程将mRNA逆转录到新的基因组位置进行繁殖。
附：英文原文
Title: Structural mechanism of LINE-1 target-primed reverse transcription
Author: George E. Ghanim, Hongmiao Hu, Jerome Boulanger, Thi Hoang Duong Nguyen
Issue&Volume: 2025-03-06
Abstract: Long interspersed element-1 (LINE-1) retrotransposons are the only active autonomous transposable elements in humans. They propagate by reverse transcribing their mRNA into new genomic locations by a process called target-primed reverse transcription (TPRT). Here, we present four cryo-electron microscopy structures of the human LINE-1 TPRT complex, revealing the conformational dynamics of ORF2p and its extensive remodeling of the target DNA for TPRT initiation. We observe nicking of the DNA second strand during reverse transcription of the first strand. Structure prediction identifies high-confidence binding sites for LINE-1-associated factors, namely PCNA and PABPC1, on ORF2p. Together with our structural data, this suggests a mechanism by which these factors regulate retrotransposition and proposes a model for TPRT that accounts for retrotransposition outcomes observed in cells.
DOI: ads8412
Source: https://www.science.org/doi/10.1126/science.ads8412