# Regulation of Leaderless mRNA Translation in Bacteria
## 3 Regulation of lmRNA Translation
Low concentrations enhance lmRNA translation, but an increased concentration of this factor inhibits protein production from some lmRNAs [19; 20]. Supporting this effect, \begin{table}
\begin{tabular}{c c c c} \hline \hline  & **SD Led Initiation** & **Leaderless Initiation** & **References** \\ \hline \(5^{\prime}\) UTR & Essential for ribosome binding & Inhibits ribosome binding & [1; 5; 27; 31] \\ Structures around initiation codon & Inhibit initiation & Inhibit initiation & [1; 5; 27] \\ CA repeats downstream of initiation codon & Enhance translation & Enhance translation & [13] \\ a5D & Required for translation & Dispensable, at least in some strains & [38; 39; 40] \\ \(5^{\prime}\) phosphate & No effect & Enhances translation & [30] \\ S1 and S2 & Required for translation & Mildly inhibit translation & [20; 42; 43] \\ IF1 and IF2 & Required for translation & Enhance translation & [19; 20] \\ IF3 & Required for translation & Inhibits translation & [19; 20] \\ YchF & Not required for translation & Inhibits translation & [44] \\ fMet+tRNA\({}^{\text{Met}}\) & Mildly enhances translation & Strongly enhances translation & [20] \\ (P)ppGpp & Inhibits translation & Activates translation & [41] \\ sRNA & Might stimulate or inhibit translation & Unknown & [36] \\ Riboswitches & Might stimulate or inhibit translation & Unknown & [36] \\ Proteins binding around RBS & Might stimulate or inhibit translation & Unknown & [36] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Comparison between SD-led (canonical) and leaderless translation. in vivo experiments have shown that increased expression of _inf_C (which codes for IF3) inhibits the translation of model lmRNAs and using _inf_C mutants that allow greater flexibility in initiation codon selection enhance their expression [19]. It has been proposed that these results are a consequence of the role of IF3 in discriminating against noncanonical RBS [19] or derive from its ability to enhance 70S dissociation [19; 20]. In any case, the effects of initiation factors seem to depend, to some extent, on the lmRNA sequence. For instance, although [PERSON] et al. observed increased lmRNA translation when IF2 was used [20], [PERSON] and [PERSON] observed that IF2 inhibited the association of 70S with some, but not all, lmRNAs [21]. Additionally, in contrast to reports showing that IF3 may not be required for lmRNA translation [19; 20], [PERSON] et al. showed that this is only observed when high levels of fMet-tRNAMet and mRNA are present, while, with \"normal\" concentrations, lmRNA translation requires IF3 [4] (although, as discussed in point 3, others have suggested that this would also depend on the lmRNA sequence [20]). 3.- Increased availability of initiator tRNA (fMet-tRNAMet) strongly enhances lmRNA translation, while producing only small increases in canonical translation. Under increased fMet-tRNAMet concentrations, some lmRNAs, such as _cl_ from \(\lambda\) phage, stop requiring initiation factors for translation, while other tested synthetic lmRNAs still require the presence of IFs for efficient translation [20]. Recent publications have proposed additional possibilities for the modulation of lmRNA translation. [PERSON] et al. proposed that YchF ATPase from _E. coli_ inhibits lmRNA translation [44], and we found that (p) ppGpp may activate lmRNAs translation in addition to its known role in the inhibition of canonical translation [41]. Whether these and the previously reported effects are interconnected or not is not known, but several associations may exist. For instance, the (p) ppGpp inhibition of canonical translation may lead to the accumulation of fMet-tRNAMet, which could stimulate lmRNA translation. Its binding to initiator factors [45; 46] could have a similar effect by decreasing the competition for ribosomes between canonical and lmRNA translation. A connection between YchF and initiation factors is also possible, and, in fact, [PERSON] et al. proposed that this protein regulates lmRNA production owing to its interaction with IF3 [44].