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

Tianze Guo; Olivia L Modi; Jillian Hirano; Horacio V Guzman; Tatsuhisa Tsuboi

doi:10.1016/j.bpr.2022.100065

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

Biophys Rep (N Y). 2022 Aug 5;2(3):100065. doi: 10.1016/j.bpr.2022.100065. eCollection 2022 Sep 14.

Authors

Tianze Guo¹, Olivia L Modi¹, Jillian Hirano¹, Horacio V Guzman², Tatsuhisa Tsuboi^{1

3}

Affiliations

¹ Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, California.
² Department of Theoretical Physics, Jozef Stefan Institute, Ljubljana, Slovenia.
³ Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen, Guangdong, China.

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. Here, we introduce the Three-dimensional RNA Illustration Program (TRIP) to model the three-dimensional RNA folding shape based on single-chain models and angle restriction of each bead component from previously reported single-molecule fluorescence in situ hybridization (smFISH) experimental data. This simulation method was able to recapitulate the mRNA conformation change of the translation activity and three-dimensional positional interaction between an organelle and its localized mRNAs as end-to-end distances. 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 top-down method will be used to interpret the aggregation mechanism of mRNA under different cellular conditions such as nucleolus and phase-separated granules.