## 4 The Role of YchF/Ola1 in Translation
Thus, the available data suggest that upon stress conditions, increased Ola1-levels attenuate canonical translation initiation, while simultaneously favouring alternative translation initiation mechanisms, which stimulates cell survival under stress conditions (Figure 4A). This assumption is further supported by the observation that Ola1 did not inhibit the Cap-independent translation of viral proteins [39]. Translation of viral proteins is often initiated by mRNA elements called internal ribosome binding sites (IRES) [97], but IRES-based initiation is also frequently used for translating stress response proteins [98]. Translation initiation in bacteria deviates from initiation in eukaryotes and starts with the formation of an instable 30S pre-initiation complex. This complex contains the initiation factors (IF) IF1, IF2 and IF3, the fMet-tRNA(Mot) and the mRNA, which is bound via its Shine-Dalgarno sequence to the anti-Shine-Dalgarno sequence within the 16S rRNA of the 30S subunit [85; 99]. The recognition of the AUG start codon by the fMet-tRNA(Mot) induces a conformational change that converts the 30S pre-initiation complex into the 30S initiation complex. Due to the conformational change, IF3 is destabilized and dissociates, allowing the recruitment of the 50S subunit and transition of the 30S initiation complex to the 70S initiation complex [100]. Dissociation of IF3 also weakens ribosome binding of IF1 and IF2, which dissociate during transition to the 70S initiation complex [85]. Similar to eukaryotes, bacteria engage alternative translation initiation mechanisms, and they are particularly important for those mRNAs that lack the Shine-Dalgarno sequence. The occurrence of these leaderless mRNAs (ImRNAs) is highly variable between species [101; 102]. They are highly abundant in _Deinococcus deserti_ (47% of all mRNAs) and their translation is linked to the extreme stress resistance of this species [103]. lmRNAs are also frequently observed in _Mycobacterium spec._ (33% in \(M\). _avinum_) and expressed when cells encounter stress conditions [104; 105; 106]. In the halophilic archaeon _Haloferax volcanii_ about 72% of all mRNAs are leaderless [107; 108; 109]. In proteobacteria, such as _E. coli_, the percentage of naturally occurring lmRNAs is rather low (0.7% in _E. coli_ BW25113) [101; 110], but they can be generated by post-transcriptional processing of canonical mRNAs, e.g., by the ribonuclease MazF [111; 112]. MazF constitutes the toxin of the MazEF toxin-antitoxin system [113; 114]. Upon stress conditions, the labile anti-toxin MazE is proteolized and MazF is released for mRNA degradation [115; 5; 113]. Although MazF predominantly degrades mRNAs completely [116; 117], it can also generate lmRNAs by cleaving off the Shine-Dalgarno sequence [111]. Among the predicted MazF targets are many mRNAs encoding for stress response proteins [112], which supports the idea that selective lmRNA translation is an important cornerstone of stress adaptation [118; 5]. Due to the absence of the Shine-Dalgarno sequence, the AUG initiation codon at the very 5\({}^{\prime}\)-end of the mRNA serves as a major signal for ribosome binding to these lmRNAs. However, in some bacterial species, including Bacteroidetes and Cyanobacteria, mRNAs contain a 5\({}^{\prime}\)-leader sequence without clearly recognizable Shine-Dalgarno motifs and their initiation is at least partially determined by the RNA structure around the initiation codon [119; 120; 121; 110]. Most studies indicate that translation of mRNAs starting with the AUG start codon is initiated on 70S ribosomes in bacteria [101]. This is deduced from the observation that 70S ribosomes bind lmRNAs with higher affinity than 30S subunits [122] and that the stability of the 70S initiation complexes increased in the presence of lmRNAA [123]. Translation of canonical mRNAs, but not that of lmRNAs, is inhibited by chemical cross-linking or by inactivation of ribosome recycling factors, which prevent dissociation of the 70S ribosome [124].