近日，德国慕尼黑路德维希马克西米利安大学Stefan H. Stricker及其团队研制了通过CRISPR激活rRNA转录来操纵蛋白质翻译和干细胞自我更新。这一研究成果发表在2026年7月2日出版的国际学术期刊《科学》上。

课题组研究人员开发了TAPIR (Targeted Activation of Protein Translation)，这是一种基于CRISPR的方法，通过诱导47S rDNA转录来提高rRNA水平。即使在快速增殖的细胞中，TAPIR也增加了核仁大小和蛋白质合成。在神经干细胞中，升高的翻译促进了体外和体内的自我更新和增殖。

此外，TAPIR能够建模和部分修复相关的疾病表型。他们的发现揭示了rRNA水平直接调节翻译输出，蛋白质合成能力可以作为哺乳动物干细胞行为的关键决定因素。

据了解，核糖体RNA （rRNA）转录率在发育过程中变化，其失调与癌症和核糖体病等疾病有关。由于它们的高丰度和基因组冗余，rRNA水平的功能意义尚不清楚。

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, Jovica Ninkovic, Rico Schieweck, Markus Diefenbacher, Stefanie M. Hauck, Paul Trainor, Faraz K. Mardakheh, Magdalena Gtz, Stefan H. Stricker

Issue&Volume: 2026-07-02

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. Here, we developed TAPIR (Targeted Activation of Protein Translation), a CRISPR-based approach to elevate rRNA-levels by inducing 47S rDNA 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 revealed that rRNA-levels directly regulate translational output and that protein synthesis capacity can act as a key determinant of mammalian stem cell behavior.

DOI: aeh1348

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

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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