# Regulation of Leaderless mRNA Translation in Bacteria
## 4 Regulation of the Expression of Specific Genes by lmRNA Translation  
Most of the reported mechanisms that could alter the efficiency of lmRNA translation are rather general, affecting all lmRNAs at the same time. Although it has been observed that, for many of these effects, there is some impact of the sequence on the intensity of lmRNA translation enhancement, an important question remains as to whether lmRNA translation allows for the regulation of the expression of particular genes or if only global changes to gene translation are possible. In enterobacteria such as _E. coli_, only a small number of lmRNAs have been found to be expressed under control conditions. For instance, one deep sequencing study found only 20 to 30 lmRNAs in the _E. coli_ transcriptome [52]. Thus, increased global lmRNA translation combined with the activation of a subgroup of promoters that enhance lmRNA transcription could be enough to elicit specific responses. For instance, in _Shigella flexneri_, a promoter located within the _virF_ coding sequence has been found to control the transcription of a shorter version of VirF (Virf\({}_{21}\)). VirF is a transcription factor that controls the pathogenicity of _Shigella_, and VirF\({}_{21}\) has been found to repress the transcription of the long version of _virF_[53]. Thus, increased transcription of _virF\({}_{21}\)_ coupled with enhanced translation of all lmRNAs could potentially modulate pathogenicity, even if lmRNA translation activation is general and not specific. In contrast to enterobacteria, in which only a small number of lmRNAs have been observed, in other bacteria, a much greater fraction of the transcriptome corresponds to lmRNAs. For example, transcriptomic studies suggest that in _Mycobacterium smegmatis_[25], _Mycobacterium tuberculosis_[54], and _Streptomyces coelicolor_[55], around 20 to 25% of the genes depend on lmRNA translation, while in organisms such as _Deinococcus deserti_[56], this number increases to around 60% of the genes. It has been proposed that this important variation in the number of lmRNAs found in diverse species is inversely correlated with the number and length of operons in the corresponding genomes [57]. In species with large numbers of lmRNAs, one would expect that there would be a mechanism to specifically regulate the translation of some genes, as global changes would otherwise alter the translation of too many genes to allow specific adaptation to each possible environmental change. Given that lmRNA presents very few, if any, nucleotides upstream of the initiation codon, it is unlikely that we will find riboswitches controlling lmRNA translation, unless they are located within the coding sequence. Nevertheless, there is no obvious reason to think that we will not find proteins or small RNAs that bind to lmRNAs, altering the accessibility of these RNAs for the translation apparatus. It is also plausible that the chemical modification of the 5\({}^{\prime}\) ends of lmRNAs through bacterial capping with NADH [58], Np4 [59; 60; 61], or other molecules [62] might alter translation efficiency. Although, to our knowledge, there are no reports of such regulation strategies, we do know that lmRNA translation could specifically regulate the translation of downstream genes. [PERSON] et al. proposed that small leaderless open reading frames can regulate the translation of downstream genes using a strategy that is similar to uORFs in eukaryotic cells. In fact, they showed that 5\({}^{\prime}\) \"untranslated\" regions in _E. coli_ beginning with AUG can alter the translation efficiency for the genes immediately downstream [6; 22; 63]. Furthermore, [PERSON] et al. showed that similar small lmRNA ORFs found in _M. smegmatis_ and containing contiguous cysteine codons could regulate the translation of downstream genes through an attenuation mechanism in which the speed of ribosome elongation depends on the availability of cysteine [64].