Molecular Cell
05 January 2023
CRISPR-free, programmable RNA pseudouridylation to suppress premature termination codons
Jinghui Song1,9,10, Liting Dong1,2,9 ,Hanxiao Sun1,9 ,Nan Luo1,9 ,Qiang Huang1,9 ,Kai Li1,2,3 ,Xiaowen Shen2 ,Zhe Jiang1 ,Zhicong Lv1 ,Luxin Peng4 ,Meifang Zhang5 ,Kun Wang1 ,Ke Liu6 ,Jiaxu Hong7 ,Chengqi Yi1,2,8,*
1 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, PRC
2 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, PRC
3 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, PRC
4 College of Chemistry and Molecular Engineering, Peking University, Beijing, PRC
5 Elpis Biotechnology Company Limited, Beijing, PRC
6 Department of Otolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, PRC
7 Department of Ophthalmology, Eye and Ear, Nose, Throat Hospital of Fudan University, Shanghai, PRC
8 Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, PRC
9 These authors contributed equally
10 Present address: Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
10.1016/j.molcel.2022.11.011
This image depicts a traditional Chinese fable of “adding eyes to a dragon.” When Zhang Sengyao, a famous Chinese painter in the Liang Dynasty, added the missing eyes to a painted dragon (resembling a single-stranded mRNA) on the wall, it came to life and flew into the clouds, demonstrating the idea that solving crucial points will lead to breakthrough. At the same time, the dragon is an essential element of the Spring Festival, which represent the Chinese people’s expectation for a better life. In this issue of Molecular Cell, Song et al. (139–155) report a CRISPR-free, programmable RNA base editor—RESTART—to specifically suppress PTC-induced translation termination. RESTART leverages the H/ACA box snoRNP machinery (the paintbrush) for RNA targeting (dragon) and pseudouridylation (eyes). The pseudouridine (Ψ)-edited PTCs are then read through, much like bringing the dragon to life.
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