{"id":495,"title":"CRISPR mutagenesis of the MYC locus reveals a druggable ultraconserved RNA element","title_zh":"CRISPR 饱和突变绘制 MYC 基因座功能图谱并鉴定可成药超保守 RNA 元件","url":"https://doi.org/10.1016/j.cell.2026.10.002","doi":"10.1016/j.cell.2026.10.002","pmid":null,"journal":"Cell","kind":"paper","lang":"en","published_at":"2026-11-01T00:00:00+00:00","fetched_at":"2026-11-08T03:45:21+00:00","authors":["Peiguo Shi","Feiyue Yang","Tala FNU","Wesley Huang","Linqing Xing","Shah Alam","Wangyang Dai","Alexis O. Aparicio","Colin H. Kalicki","Aditi Trehan","Michael R. Murphy","Esther R. Rotlevi","Prajish Iyer","Lili Wang","Sara Zaccara","Muredach P. Reilly","Ya Cheng Liao","Chaolin Zhang","Jianwen Que","Xuebing Wu"],"primary_topic":"ethics-policy","topics":[{"slug":"ethics-policy","score":3.0,"hits":["crispr"]}],"topic_score":3.0,"preference_score":0.0,"preference_labels":[],"llm_score":46.0,"final_score":58.0,"score_dims":{"novelty":86,"rigor":78,"impact":22,"relevance":12,"translation":18},"recommend_reason":"方法学上具有示范意义：以碱基分辨率解析整条基因座的功能必需位点，并证明非编码 RNA 元件可成药，对多组学筛选设计有借鉴价值；但研究对象为肿瘤细胞与类器官，与生殖医学、胚胎研究和 ART 实验室无直接关联，不建议作为本领域的优先阅读。","keywords":["CRISPR 突变扫描","MYC 基因座","非编码 RNA 元件","超保守元件","肿瘤类器官","功能基因组学"],"selected":0,"story_id":222,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"crossref-cns","source_name":"Crossref · CNS 与大子刊新上线（领域过滤）","source_tier":1,"mention_count":2,"has_interpretation":false,"journal_key":"cell","journal_tier":"cns","journal_if":45.5,"is_mock":false,"summary_zh":"研究对人类 MYC 基因座 10 kb 区域进行 CRISPR 覆盖式突变扫描，以碱基对分辨率构建整条基因的功能适应性图谱。结果显示，67% 的功能必需碱基对位于非编码区，并鉴定出一个超保守 RNA 调控元件；该元件控制 MYC 的定位，在患者来源肿瘤类器官中靶向它可抑制癌细胞生长，提示其具备成药潜力。原文为期刊论文摘要，样本量、统计方法与脱靶评估等细节未在可见信息中给出。","summary":"CRISPR tiling mutagenesis of the 10-kb human MYC locus mapped the fitness landscape of an entire human gene at base-pair resolution. This unbiased interrogation revealed that 67% of functionally essential base pairs are noncoding. An ultraconserved RNA regulatory element was identified that controls MYC localization and can be therapeutically targeted to suppress cancer cell growth in patient-derived tumor organoids.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}