Modeling alternative translation initiation sites in plants reveals evolutionarily conservedcis-regulatory codes in eukaryotes

Abstract

AbstractmRNA translation relies on identifying translation initiation sites (TISs) in mRNAs. Alternative TISs are prevalent across plant transcriptomes, but the mechanisms for their recognition are unclear. Using ribosome profiling and machine learning, we developed models for predicting alternative TISs inArabidopsis thalianaand tomato (Solanum lycopersicum). Distinct feature sets were predictive of AUG and non-AUG TISs in 5′ untranslated regions and coding sequences, including a novel CU-rich sequence that promoted plant TIS activity, a translational enhancer found across dicots and monocots and also in humans and viruses. Our results elucidate the mechanistic and evolutionary basis of TIS recognition, wherebycis-regulatory RNA signatures affect start site selection. The TIS prediction model provides global estimates of TISs to discover neglected protein-coding genes across plant genomes. The prevalence ofcis-regulatory signatures across eukaryotes and viruses suggests their broad, critical roles in reprogramming the translational landscape in the plant–virus arms race.TeaserNew insights into how plant ribosomes distinguish AUG and non-AUG triplets for protein synthesis via a conserved eukaryoticcis-regulatory strategy.