# Regulation of Leaderless mRNA Translation in Bacteria
## 3 Regulation of lmRNA Translation  
Although there are some contradictory results [5; 34], initiation is considered the slowest step of translation for most genes and, thus, the step where translation regulation is most frequently observed [5; 35]. In fact, canonical initiation may be regulated through diverse strategies at this stage. For instance, there are RNAs that alter their structure in  
Figure 2: Control of lmRNA translation. It has been observed that several factors or leaderless mRNA (lmRNA) properties may alter lmRNA translation efficiency. Shown at the top are lmRNA properties that enhance (green) or repress (red) lmRNA translation, and at the bottom are other factors that alter lmRNA translation, probably through interaction with ribosome. Dotted lines indicate factors where changing conditions or strains produce discordant results. Please refer to main text for full details regarding each case. Models of ribosomal and RNA structures were constructed using PYMOL molecular graphics system [32] and pdb 4V9M [33]. response to changes in the concentrations of some metabolites. The modification of such structures, called riboswitches, may alter the accessibility of the RBS for 30S, consequentially modifying the efficiency of translation initiation. The binding of small RNAs or proteins to or near the RBS may also alter its accessibility for 30S producing similar effects on translation efficiency [35; 36]. Although the mechanisms involved in the regulation of canonical initiation are well described, we do not have a good description of lmRNA translation regulation. [PERSON] et al. proposed that, in _E. coli_, lmRNA translation could be regulated by the cleavage the 16S rRNA. In their model, under stress conditions, the MazF toxin was activated due to decreased transcription and/or translation, coupled to the faster degradation of its antitoxin, MazE. As MazE was rapidly degraded, the remaining MazF led to the cleavage of 16S rRNA. As a consequence, the ribosome lost the a5D sequence (or at least its functionality [37]) and, with it, the possibility of binding canonical mRNAs to initiate translation [38]. It was proposed that, as a consequence, mostly lmRNAs would be translated under such conditions. Additionally, some lmRNAs could be formed by a similar MazF-dependent cleavage of canonical mRNAs. Thus, MazF activation would lead to the formation of lmRNAs and \"stress ribosomes\" that would specifically translate such mRNAs [38]. Unfortunately, other laboratories have not been able to reproduce these findings, either by MazF over-expression [39; 40] or under natural stress conditions that enhance lmRNA translation [41]. Consequently, we must assume that the MazF dependent regulation of lmRNA translation is not as widespread as originally proposed. Before the MazF model for the regulation of lmRNA translation was proposed, published results pointed in a different direction, as in vitro and some in vivo experiments suggested that alterations to the concentration or activity of diverse components of the translation apparatus could enhance lmRNA translation to the detriment of canonical translation (Figure 2 and Table 1). These early results can be summarized as follows:  
* bS1 and other ribosomal proteins, such as uS2 (previously S2 [8]), are not required for the translation of lmRNAs [11; 20; 42; 43]. Although there is a small decrease in in vitro translation with the loss of these proteins, increased translation is observed in vivo when they are lost (e.g., because of a temperature-sensitive mutation of the uS2 coding gene, _rpsB_). This is probably a consequence of the loss of the ability to translate canonical mRNAs that, under \"normal\" conditions, would compete for available ribosomes [43]. * In vitro results indicate that translation initiation factors are not essential for lmRNA translation, but the process is usually stimulated by their presence. While IF1 and IF2 stimulate lmRNA translation in vitro at any concentration, IF3 has a dual effect.