Comprehensive Summary
The present study by González et al. explores the use of steady state and dynamic multi-omics data from human liver cell lines to further determine the affecting factors in mRNA translation rates. HepG2 and Huh7 human liver cell lines were maintained for the experiment and a complimentary technique of ribosomal sequencing (ribo-seq), polysome profiling followed by RNA-seq, and protein synthesis rate determination with pSILAC. Ribo-seq allowed for the tracking of ribosomal progression over time and a stable estimation of elongation speed of the transcript, and polysome profiling allowed for the determination of the mean ribosome load per mRNA synthesized. The study confirmed a weak correlation between the level of mRNA present and the observed protein output, and thus reinforces the need to understand study translation mechanisms beyond transcript abundance. Additional findings note the initiation phase of translation as the rate-limiting step for transcription rates, and the limited explanation for observed translation rates offered by known determinants including codon usage and UTR elements. The study further highlights the need for machine learning to be utilized in analyzing rich datasets to better understand how mRNA structure and sequence determines protein output.
Outcomes and Implications
The use of machine learning in analyzing large datasets, namely cell line sets, allows for the streamlining rationale for mRNA-based vaccines and related therapeutics. The multi-omic assessment methodology, when applied to other human organs or body systems, presents the chance to form a stronger understanding of transcriptional rates and the regulatory factors that are behind them. It will take much more time for extensive research and further exploration of undiscovered regulatory transcription mechanisms to fully qualify new mRNA-based therapeutics and vaccines for commercial use in medical spaces.