BPS2026 – Variable 1D sequences and conserved 2D/3D structures of DNA-packaging ATPase-driving ncRNA nanostructures for tracking the evolution and origin of organisms—Discovery of 12 new ncRNA-nanostructures for developing and delivering potent therapeutics

Microorganisms are continually mutating and evolving. Here, we apply nanotechnology to discover that ncRNAs’ 1D sequences vary widely while their 2D and 3D are highly conserved or covary. The recent discovery that RNA nanoparticles are motile, supports the hypothesis that RNA holds certain features of living systems. Previously, we reported a class of small RNA (sRNA) with novel function (Guo et al., Science . 1987. PMID:31071240). Structure studies of this ATPase motor-gearing pRNA have led to the emergence of the new field of RNA Nanotechnology (Guo P. and colleagues, Nature Nanotechnology , 2010. PMID:21102465; Nature Nanotechnology , 2011. PMID:21909084). Phi29 infects the spore-forming Bacillus subtilis , which can be long hidden in the soil without be subjected to evolutionary changes due to the protection of spores. Thus, they serve as living fossils. We searched for more pRNAs, but their 1D diversity made it challenging to search by alignment. But application of 2D and 3D algorithms identified 12 new ncRNAs with variable 1D but conserved 2D and 3D structures. The stoichiometry of the pRNAs is a multiple of 2 and 3, which is 6. Mimicking the series circuits of “Christmas light bulbs” and based on the finding that the dsDNA packaging motors, the ABC drug-transporters, and the ATP-producing ATPase are very similar in structure, with multi-homosubunit and a sequential revolving mechanism. We therefore developed several potent therapeutics following the “Christmas light bulb series circuit” strategy. Here, blocking a single bulb will inhibit the entire lighting strand, as described by the formula x=(p+q) z =∑ZM=0(ZM)pZ−MqM=∑ZM=0(Z!M!(Z−M)!)pZ−MqM.