基于深度突变扫描在人类基因组中发现的最小自剪切核酶

Minimal twister sister-like self-cleaving ribozymes in the human genome by deep mutational scanning

摘要：本报告通过深度突变扫描技术，在人类基因组中发现了两类最小的螺旋姐妹型(twister sister-like)自剪切核酶——LINE-1-rbz 和 OR4K15-rbz。研究采用新型计算方法（CODA）分析高通量数据，确定这两类核酶是迄今已知最小的核酶，二者互为环状置换变体，并共享一个简单且可能为原始形态的结构核心。生化实验验证了其催化机制与离子依赖性。这类最小化的反式剪切核酶结构，表明其在基因敲低和RNA疗法方面具有重要潜在应用价值。

ABSTRACT: This presentation details the discovery of two minimal, twister sister-like self-cleaving ribozymes—LINE-1-rbz and OR4K15-rbz—within the human genome, identified through deep mutational scanning. Using a novel computational method (CODA) to analyze the high-throughput data, the study determined these ribozymes are the shortest known, are circular permutations of one another, and share a simple, likely primitive structural core. Biochemical validation confirmed their catalytic mechanism and ion dependence. Their minimal, trans-cleaving architecture suggests significant potential for applications in gene knockdown and RNA-based therapeutics.

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