Single chain models illustrate the 3D RNA folding shape during translation

Abstract

The three-dimensional conformation of RNA is important in the function and fate of the molecule. The common conformation of mRNA is formed based on the closed-loop structure and internal base pairings with the activity of the ribosome movements. However, recent reports suggest that the closed-loop structure might not be formed in many mRNAs. This implies that mRNA can be considered as a single polymer in the cell. We developed TRIP; Three-dimensional RNA Illustration Program, to model the three-dimensional RNA folding shape based on single-chain models. We identified the angle restriction of each bead component from previously reported single-molecule FISH experimental data. This simulation method was able to recapitulate the mRNA conformation change of the translation activity and three-dimensional positional interaction between organelle and its localized mRNAs. Within the analyzed cases base-pairing interactions only have minor effects on the three-dimensional mRNA conformation, and instead single-chain polymer characteristics have a more significant impact on the conformation. This method will be used to predict the aggregation mechanism of mRNA and long noncoding RNA in specific cellular conditions such as nucleolus and phase-separated granules.