Trends in Genetics
Volume 29, Issue 2, February 2013, Pages 92-98
Journal home page for Trends in Genetics

Review
New insights into small RNA-dependent translational regulation in prokaryotes

https://doi.org/10.1016/j.tig.2012.10.004Get rights and content

Bacterial small RNAs (sRNAs) typically repress translation of target mRNAs by pairing directly to the ribosome-binding site (RBS) and competing with initiating ribosomes, an event that is often followed by rapid mRNA decay. In recent years, however, many examples of translation-repressing sRNAs pairing outside the RBS have been described. In this review, we focus on newly characterized mechanisms that explain how a sRNA can modulate translation by binding outside of the RBS and discuss new insights into the events following translation repression. These new mechanisms broaden current perspectives of sRNA pairing sites on mRNA targets and demonstrate how the interplay between sRNAs, mRNA structures, and protein partners can contribute to post-transcriptional regulation.

Section snippets

Small RNAs in bacteria

When they were first characterized in 1984, bacterial sRNAs were the first example of a trans-acting regulator controlling translation of specific mRNAs through an antisense mechanism [1]. Since this seminal discovery, sRNA-based regulation has been shown to play major roles in a wide range of organisms, from bacteria to humans. In bacteria such as Escherichia coli, where more than 80 sRNAs have been identified [2], sRNAs have been shown to help cells adjust to environmental pressures by

Translation initiation in bacteria

During protein synthesis, translation initiation is the most rate-limiting and highly regulated step [14]. The canonical model for prokaryotic translation initiation involves mRNA recognition by the 30S subunit of the ribosome, which is mediated by RNA–RNA base-pairing interactions. The 3′-terminal sequence of the 16S rRNA AUCACCUCCUUA (termed antiSD) base-pairs with the purine-rich Shine-Dalgarno (SD) sequence of mRNA [15]. The antiSD–SD base-pairing directs the initiation codon to the P site

sRNAs competing with a ribosome standby site

The first example of translation repression by a non-canonical mechanism was described as occurring through the action of a cis-acting antisense RNA, which does not rely on Hfq for activity [36]. In this study, the authors showed that the antisense RNA IstR-1 represses the translation of the tisB mRNA, which encodes a protein involved in a toxin–antitoxin system, by binding to a ribosome standby site located approximately 100 nucleotides upstream of the RBS (Figure 2a). Ribosome standby sites

To degrade or not to degrade?

As stated above, translation repression by bacterial sRNAs is often followed by rapid decay of the mRNA (nucleolytic repression). However, in some cases, there is an absence of rapid degradation of the mRNA following the block of translation (non-nucleolytic repression) 10, 42, 48, 49, 52. The reasons for this dichotomy are not totally understood, but recent studies have shed some light on this question.

For example, one particularly interesting case is the sRNA-mediated regulation of sdhCDAB

Concluding remarks

The recent characterization of sRNA-regulated mRNAs has suggested an unexpected array of singular mechanisms in which structures strictly related to mRNAs (and not sRNAs) are involved. Indeed, one common feature among these novel mechanisms is the unsuspected contribution of mRNA features to the mechanisms regulating these targeted mRNAs, such as distal cleavage sites. This interpretation is supported by another description of critical structures specifically adopted by target mRNAs that are

Acknowledgments

We thank Hubert Salvail and Gilles Dupuis for editorial comments. Work in our laboratory was funded by an operating grant MOP69005 to EM from the Canadian Institute for Health Research. GD is a PhD scholar from the Fonds Québécois de la Recherche sur la Nature et les Technologies. EM is a Fonds de Recherche Santé Québec Senior scholar.

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