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Cell:高彩霞/刘俊杰/张勇等揭示CRISPR系统起源的关键分子机制
生物世界· 2025-09-29 23:30
Core Insights - The article discusses the evolutionary emergence of type V CRISPR-Cas systems from transposons, highlighting the discovery of a key evolutionary intermediate named TranC, which bridges the gap between transposons and CRISPR systems [3][11]. Group 1: Research Findings - The research team identified 146 CRISPR candidate proteins closely related to TnpB through a combination of sequence similarity, shared structural domain features, and conserved catalytic motifs [6]. - Six evolutionary intermediate families were identified and named TranC, representing multiple independent evolutionary paths from TnpB to Cas12 [6][7]. - The study revealed that the core mechanism driving the evolution of TnpB transposase to the Cas12 system is the "functional splitting" of guide RNA, rather than fundamental changes in protein structure [3][11]. Group 2: Functional Mechanisms - The TranC system exhibits a unique "dual RNA guiding mechanism," allowing it to utilize both its own CRISPR RNA and ancestral TnpB-derived RNA for targeted cutting [7]. - Structural biology analysis showed that the TranC protein is highly conserved in three-dimensional structure compared to its ancestor TnpB, with differences primarily at the RNA level [8]. - The research demonstrated that the transition from a single RNA-guided TnpB mechanism to a dual RNA-guided CRISPR mechanism can be achieved by functionally splitting the reRNA module [9]. Group 3: Applications and Innovations - The LaTranC genome editing system was engineered to create a high-efficiency variant, TranC11a, which outperforms existing small nucleases and shows comparable editing efficiency to SpCas9 in certain loci [12]. - TranC series core patents have passed the Freedom to Operate (FTO) review, laying a solid foundation for its application in biomedicine and agricultural breeding [13].