Recognition of RNA secondary structures with a programmable peptide nucleic acid-based platform
RNA secondary structures comprise double-stranded (ds) and single-stranded (ss) regions. Antisense peptide nucleic acids (asPNAs) enable the targeting of ssRNAs and weakly formed dsRNAs. Nucleobase-modified dsRNA-binding PNAs (dbPNAs) allow for dsRNA targeting. A programmable RNA-structure-specific targeting strategy is needed for the simultaneous recognition of dsRNAs and ssRNAs. Here, we report on combining dbPNAs and asPNAs (designated as daPNAs) for the targeting of dsRNA-ssRNA junctions. Our data suggest that combining traditional asPNA (with a 4-letter code: T, C, A, and G) and dbPNA (with a 4-letter code: T or s2U, L, Q, and E) scaffolds facilitates RNA-structure-specific tight binding (nM to μM). We further apply our daPNAs in substrate-specific inhibition of Dicer acting on precursor miRNA (pre-miR)-198 in a cell-free assay and regulating ribosomal frameshifting induced by model hairpins in both cell-free and cell culture assays. daPNAs would be a useful platform for developing chemical probes and therapeutic ligands targeting RNA.
Authors
- Zhenyu Meng (ORCID: https://orcid.org/0000-0002-9554-9359)
- Guobao Li (ORCID: https://orcid.org/0000-0003-3061-193X)
- Desiree‐Faye Kaixin Toh
- Kiran M. Patil (ORCID: https://orcid.org/0000-0002-9887-128X)
- Liping Deng (ORCID: https://orcid.org/0000-0002-7651-0096)
- Huan‐Xiang Zhou (ORCID: https://orcid.org/0000-0001-9020-0302)
- Yunpeng Lu (ORCID: https://orcid.org/0000-0003-2493-7853)
- Alan Ann Lerk Ong
- Gang Chen (ORCID: https://orcid.org/0000-0002-8772-9755)
- Lizhe Zhu (ORCID: https://orcid.org/0000-0001-8252-7807)
- Xuan Zhan (ORCID: https://orcid.org/0000-0003-1444-9194)
- Lixia Yang (ORCID: https://orcid.org/0000-0002-2188-3485)
- Xin Ke (ORCID: https://orcid.org/0000-0002-5860-5366)
- Rongguang Lu (ORCID: https://orcid.org/0000-0003-1737-3594)
- Hongwei Wang (ORCID: https://orcid.org/0000-0003-3581-8892)
- Zheng Liu (ORCID: https://orcid.org/0000-0002-3538-9349)
- Yining Liu (ORCID: https://orcid.org/0009-0006-4253-0546)
- Manchugondanahalli S. Krishna (ORCID: https://orcid.org/0000-0003-1907-6809)
- Shijian Fan
- Kun Xi (ORCID: https://orcid.org/0000-0003-1650-0002)
- Yanyu Chen (ORCID: https://orcid.org/0009-0008-8801-1316)
- Yun Lian
- Ruiyu Lin
Institutions
- University of Electronic Science and Technology of China (CN)
- Nanyang Technological University (SG)
- Chinese University of Hong Kong, Shenzhen (CN)
- Shenzhen Third People’s Hospital (CN)
- Tsinghua University (CN)
Publication Details
- Journal
- Cell Reports Physical Science
- Published
- 2024-08-12
- DOI
- https://doi.org/10.1016/j.xcrp.2024.102150
- Citations
- 8
- Primary Topic
- RNA and protein synthesis mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 1.87