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-Structure paper
タイトル | Hydrolytic endonucleolytic ribozyme (HYER) is programmable for sequence-specific DNA cleavage. |
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ジャーナル・号・ページ | Science, Vol. 383, Issue 6682, Page eadh4859, Year 2024 |
掲載日 | 2024年2月2日 |
著者 | Zi-Xian Liu / Shouyue Zhang / Han-Zhou Zhu / Zhi-Hang Chen / Yun Yang / Long-Qi Li / Yuan Lei / Yun Liu / Dan-Yuan Li / Ao Sun / Cheng-Ping Li / Shun-Qing Tan / Gao-Li Wang / Jie-Yi Shen / Shuai Jin / Caixia Gao / Jun-Jie Gogo Liu / |
PubMed 要旨 | Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA ...Ribozymes are catalytic RNAs with diverse functions including self-splicing and polymerization. This work aims to discover natural ribozymes that behave as hydrolytic and sequence-specific DNA endonucleases, which could be repurposed as DNA manipulation tools. Focused on bacterial group II-C introns, we found that many systems without intron-encoded protein propagate multiple copies in their resident genomes. These introns, named HYdrolytic Endonucleolytic Ribozymes (HYERs), cleaved RNA, single-stranded DNA, bubbled double-stranded DNA (dsDNA), and plasmids in vitro. HYER1 generated dsDNA breaks in the mammalian genome. Cryo-electron microscopy analysis revealed a homodimer structure for HYER1, where each monomer contains a Mg-dependent hydrolysis pocket and captures DNA complementary to the target recognition site (TRS). Rational designs including TRS extension, recruiting sequence insertion, and heterodimerization yielded engineered HYERs showing improved specificity and flexibility for DNA manipulation. |
リンク | Science / PubMed:38301022 |
手法 | EM (単粒子) |
解像度 | 2.58 - 3.41 Å |
構造データ | EMDB-36776, PDB-8k0p: EMDB-36777: The Anoxybacillus pushchinoensis ORF-less Group IIC Intron DR1 at symmetric pre-cleavage state EMDB-36778, PDB-8k0r: EMDB-36779, PDB-8k0s: EMDB-36786, PDB-8k15: |
化合物 | ChemComp-MG: |
由来 |
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キーワード | RNA / ORF-less Group IIC intron / ribozymes |