北京大学最新Cell论文：刘君团队开发全转录组单个m6A位点功能筛选工具——FOCAS，揭开m6A在癌症中的复杂性和治疗意义

Core Viewpoint - The article discusses the development of a novel high-throughput screening technology called FOCAS, which enables the functional dissection of individual m6A sites in mRNA, significantly enhancing the understanding of m6A's role in gene expression regulation, particularly in cancer [3][11]. Group 1: m6A Modification and Its Importance - m6A is the most prevalent chemical modification in mRNA, regulating gene expression without altering RNA sequences [2]. - The m6A modification process is controlled by three types of proteins: "Writers" (METTL3/METTL14 complex), "Erasers" (FTO, ALKBH5), and "Readers" (YTHDF family proteins) [2]. Group 2: FOCAS Technology Development - FOCAS is based on the CRISPR-dCas13b system and FTO, allowing for high-throughput, site-specific functional screening of m6A [4][8]. - This technology provides a powerful and unbiased method for functional analysis of m6A, laying a solid foundation for future basic research and therapeutic development [4][11]. Group 3: Key Findings from the Research - A total of 4,475 genes were identified whose expression is regulated by m6A across four cancer cell lines, affecting cell survival and proliferation [9]. - Many identified m6A-regulated genes are newly associated with cancer, exhibiting dynamic expression changes [9]. - The role of m6A within the same gene varies depending on the cellular environment and the "Reader" proteins involved, indicating a complex regulatory mechanism [9]. - The study identified "universal" m6A patterns present in all cell lines, particularly in transcription-related genes, and "specific" m6A patterns unique to certain cell types, especially in non-coding RNAs [9]. - An extensive interaction network between the m6A modification layer and the gene expression layer was revealed in the SMMC-7721 human liver cancer cell line [9].