Comprehensive translational profiling and STE AI uncover rapid control of protein biosynthesis during cell stress

Horvath, A; Janapala, Y; Woodward, K; Mahmud, S; Cleynen, A; Gardiner, EE; Hannan, RD; Eyras, E; Preiss, T; Shirokikh, NE

Author(s): Horvath, A; Janapala, Y; Woodward, K; Mahmud, S; Cleynen, A; Gardiner, EE; Hannan, RD; Eyras, E; Preiss, T; Shirokikh, NE;
Details: Publication Year 2024-07-22,Volume 52,Issue #13,Page 7925-7946
Journal Title: Nucleic Acids Research
Publication Type: Research article
Abstract: Translational control is important in all life, but it remains a challenge to accurately quantify. When ribosomes translate messenger (m)RNA into proteins, they attach to the mRNA in series, forming poly(ribo)somes, and can co-localize. Here, we computationally model new types of co-localized ribosomal complexes on mRNA and identify them using enhanced translation complex profile sequencing (eTCP-seq) based on rapid in vivo crosslinking. We detect long disome footprints outside regions of non-random elongation stalls and show these are linked to translation initiation and protein biosynthesis rates. We subject footprints of disomes and other translation complexes to artificial intelligence (AI) analysis and construct a new, accurate and self-normalized measure of translation, termed stochastic translation efficiency (STE). We then apply STE to investigate rapid changes to mRNA translation in yeast undergoing glucose depletion. Importantly, we show that, well beyond tagging elongation stalls, footprints of co-localized ribosomes provide rich insight into translational mechanisms, polysome dynamics and topology. STE AI ranks cellular mRNAs by absolute translation rates under given conditions, can assist in identifying its control elements and will facilitate the development of next-generation synthetic biology designs and mRNA-based therapeutics.
Publisher: Oxford University Press
Keywords: *Protein Biosynthesis; *RNA, Messenger/genetics/metabolism; *Ribosomes/metabolism/genetics; *Saccharomyces cerevisiae/genetics/metabolism; Polyribosomes/metabolism/genetics; Artificial Intelligence; Stress, Physiological/genetics; Glucose/metabolism; Saccharomyces cerevisiae Proteins/metabolism/genetics; Peptide Chain Initiation, Translational
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1093/nar/gkae365
Open Access at Publisher's Site: https://doi.org/10.1093/nar/gkae365
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-08-29 04:21:46

Last Modified: 2024-08-29 04:22:02