In silico analysis of 5′-UTRs highlights the prevalence of Shine–Dalgarno and leaderless-dependent mechanisms of translation initiation in bacteria and archaea, respectively

A combination of mRNA features influence the efficiency of leaderless mRNA translation initiation

“…This suggests that there are likely to be some species-specific differences in leaderless mRNA features arising from the differences in the translation initiation machinery. Indeed, across prokaryotes, 79% of predicted leaderless genes contain AUG as the start codon, whereas GUG, UUG and others are found with an average of 10%, 6% and 3% respectively (13). Surprisingly, leaderless mRNAs across organisms appear to initiate with assembled 70S/80S ribosomes (31,61–63), further suggesting a conserved mechanism of initiation.…”

“…Indeed, “orthogonal” ribosomes with altered 16S rRNA aSD sequences were found to initiate at the normal start codons throughout the transcriptome (11). Interestingly, E. coli lacks SD sites within its genome in approximately 30% of its translation initiation regions (TIRs) with other species of bacteria containing SD sites in as few as 8% of their TIRs (12,13). Indeed, RNA-seq based transcription mapping experiments have found that many bacterial mRNAs are “leaderless” and begin directly at the AUG start codon (14–16), and that these mRNAs are abundant in pathogens such as M. tuberculosis and in the mammalian mitochondria (17).…”

“…In E. coli , suppressor tRNAs could restore initiation on non-AUG codons for leadered RNAs, but not for leaderless RNAs (32), suggesting that for leaderless mRNAs an AUG start codon has unique initiation properties independent of perfect codon-anticodon base-pairing. Indeed, genomic prediction of leaderless mRNAs suggests a very high preference of AUG (79%) at the 5’ end of leaderless mRNAs; with a smaller percentage of GUG (10%), UUG (6%) and others (3%) (13). In addition to the start codon identity, TIE of mRNAs with short leaders (<5nt) is significantly lower as compared to their fully leaderless counterparts (34,35,37–39).…”

ΔGunfold leaderless, a package for high-throughput analysis of translation initiation regions (TIRs) at the transcriptome scale and for leaderless mRNA optimization

“…ΔG unfold leaderless allows users to automate the ΔG unfold calculation to perform high-throughput analysis. Importantly, ΔG unfold leaderless allows calculation of TIRs of both leadered mRNAs and leaderless mRNAs which lack a 5’ UTR and which are abundant in bacterial, archaeal, and mitochondrial transcriptomes (4, 6, 7). The ability to analyze leaderless mRNAs also allows one additional feature where users can computationally optimize leaderless mRNA TIRs to maximize their gene expression (8, 9).…”

Start Codon Recognition in Eukaryotic and Archaeal Translation Initiation: A Common Structural Core

“…The evolution of translation initiation mechanisms is also related to the evolution of the 5′ untranslated regions of mRNA. For instance, mRNAs having very short or no 5′UTRs, called leaderless mRNAs, are present in all domains of life [151,152]. Such leaderless mRNAs are abundant in some archaea such as S. solfataricus [153,154,155,156] and Haloferax volcanii [157], though less abundant in others such as P. abyssi [158] and Aeropyrum pernix [153].…”