2026年9月10日，德国慕尼黑大学Stefan H. Stricker等科学家在《科学》（Science）发表研究，通过CRISPR激活rRNA转录操控蛋白质翻译与干细胞自我更新。

核糖体RNA（rRNA）转录速率在发育过程中发生变化，其失调与癌症和核糖体病等疾病相关。由于rRNA丰度高且基因组冗余，rRNA水平的功能意义仍不清楚。研究人员开发了TAPIR（靶向激活蛋白质翻译），一种基于CRISPR的方法，通过诱导47S核糖体DNA转录来提高rRNA水平。TAPIR增加了核仁大小并增强蛋白质合成，即使在快速增殖的细胞中也是如此。在神经干细胞中，翻译水平升高促进了体外和体内的自我更新和增殖。此外，TAPIR使得相关疾病表型的建模和部分挽救成为可能。研究人员的发现揭示，rRNA水平直接调控翻译输出，并且蛋白质合成能力可作为哺乳动物干细胞行为的关键决定因素。

附：英文原文

Title: Manipulation of protein translation and stem cell self-renewal by CRISPR activation of rRNA transcription

Author: Maximilian Wiesbeck, Emilie L. Alard, Florencia Merino, Niti Chowdhury, Luisa Egert, Anna Danese, Simon Imhof, Matilde Iraci Borgia, Akshaya Rajan, Nadine Fernandez-Novel Marx, Edina Kepesidis, Anna Kferle, Luis Miguel Cerron-Alvan, Franziska Vierl, Thi-Tram Truong, Manja Thorwirth, Lorina Bilalli, André Santos Dias Mouro, Jovica Ninkovic, Rico Schieweck, Markus Diefenbacher, Stefanie M. Hauck, Paul A. Trainor, Faraz K. Mardakheh, Magdalena Gtz, Stefan H. Stricker

Issue&Volume: 2026-09-10

Abstract: Ribosomal RNA (rRNA) transcription rates vary during development, and their dysregulation is linked to diseases such as cancer and ribosomopathies. Owing to their high abundance and genomic redundancy, the functional significance of rRNA levels remains unclear. We developed TAPIR (Targeted Activation of Protein Translation), a CRISPR-based approach to elevate rRNA levels by inducing 47S ribosomal DNA transcription. TAPIR increased nucleolar size and enhanced protein synthesis, even in rapidly proliferating cells. In neural stem cells, elevated translation promoted self-renewal and proliferation in vitro and in vivo. Furthermore, TAPIR enabled the modeling and partial rescue of associated disease phenotypes. Our findings reveal that rRNA levels directly regulate translational output and that protein synthesis capacity can act as a key determinant of mammalian stem cell behavior.

DOI: 10.1126/science.aeh1348

Source: https://www.science.org/doi/10.1126/science.aeh1348