Gupta Kshitij, Parlea Lorena, Viard Mathias, Smith Katelyn, Puri Anu, Bergman Joseph T, Kim Taejin, Shapiro Bruce A
RNA Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, 21702, USA.
Present address: Genes N Life Healthcare Pvt. Ltd., Hyderabad, Telangana,500082, India.
RNA Nanomed. 2024 Dec;1(1):61-78. doi: 10.59566/isrnn.2024.0101061.
RNA can interact with positively charged, amphiphilic peptides to cooperatively assemble into fibrils that enable RNA transport across cancer cellular membranes. RNA decreases the folding energy barrier imposed by the electrostatic repulsion between these charged peptides, thus partaking in RNA-peptide self-assembly along particular pathways in the energy landscape. Specific amphiphilic peptides capable of protecting and transporting RNA across a membrane have Type II' β-turn hairpin forming motifs in their structures, which aids self-assembly into β-sheet fibrils. We employed a set of such cationic, amphiphilic peptides that have random coiled structures in the absence of folding stimuli, to characterize the (peptides):(RNA) assembly. We subjected these complexes to extensive biophysical characterization and in cell culture. We show that short RNAs (such as Dicer substrate RNAs) can lead these peptides to self-assemble into β-sheet fibrils that have RNA transport capabilities and can act as non-viral delivery vectors for RNA. Modulation in the peptide sequence implicitly alters the way they bind RNA and influence the peptides' ability to transport nucleic acids across membranes.
RNA 可与带正电荷的两亲性肽相互作用，协同组装成纤维，从而实现 RNA 跨癌细胞膜的转运。RNA 降低了这些带电荷肽之间静电排斥所施加的折叠能垒，因此在能量景观中沿着特定途径参与 RNA - 肽的自组装。能够保护和跨膜转运 RNA 的特定两亲性肽在其结构中具有 II' 型β - 转角发夹形成基序，这有助于自组装成β - 折叠纤维。我们使用了一组在没有折叠刺激时具有无规卷曲结构的阳离子两亲性肽，来表征（肽）：（RNA）组装。我们对这些复合物进行了广泛的生物物理表征并在细胞培养中进行研究。我们表明，短 RNA（如 Dicer 底物 RNA）可导致这些肽自组装成具有 RNA 转运能力的β - 折叠纤维，并且可以作为 RNA 的非病毒递送载体。肽序列的调节会隐含地改变它们结合 RNA 的方式，并影响肽跨膜转运核酸的能力。
