Nature ！中国科学家开发新型可编程的空间转录组调控技术CRISPR-TO

Core Viewpoint - The CRISPR-TO technology enables precise spatial regulation of endogenous RNA, providing a new tool for studying RNA functions and related diseases [1][2]. Group 1: Technology Overview - CRISPR-TO utilizes the Class II Type VI CRISPR-Cas13 system for spatial transcriptome regulation, allowing for targeted RNA manipulation without altering genetic sequences [3][4]. - The technology combines dCas13 with signaling peptides or motor proteins through a heterodimerization mechanism, facilitating both passive diffusion and active transport of RNA [3][4]. Group 2: Applications and Findings - CRISPR-TO successfully targets endogenous RNA to various subcellular compartments, including mitochondria, P-bodies, stress granules, telomeres, and nuclear stress bodies, enabling real-time observation of RNA dynamics in live cells [4][5]. - Targeting mRNA to P-bodies significantly reduced its degradation rate and extended its half-life, supporting the theory that P-bodies primarily serve as mRNA storage sites rather than degradation sites [4]. Group 3: Research Breakthroughs - The technology demonstrated the capability for long-distance transport of endogenous mRNA (approximately 1 mm) in primary mouse cortical neurons, allowing for the study of mRNA's cooperative effects [5][8]. - High-throughput screening using CRISPR-TO revealed that targeting Stmn2 mRNA to neurites promotes rapid neurite growth, linking it to microtubule dynamics and potential implications for ALS [8][9]. Group 4: Future Implications - CRISPR-TO bridges gaps left by existing sequencing and imaging technologies, offering a high-throughput platform for systematic studies of spatial transcriptome functions across various biological systems and disease contexts [9].