Trends in Genetics
ReviewNew insights into small RNA-dependent translational regulation in prokaryotes
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.
References (82)
- et al.
Regulatory RNAs in bacteria
Cell
(2009) - et al.
The base-pairing RNA spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli
Mol. Cell
(2011) MicroRNAs: target recognition and regulatory functions
Cell
(2009)Initiation of translation in prokaryotes and eukaryotes
Gene
(1999)An RNA thermosensor controls expression of virulence genes in Listeria monocytogenes
Cell
(2002)Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria
Cell
(2002)Small RNA binding to 5′ mRNA coding region inhibits translational initiation
Mol. Cell
(2008)How the ribosome moves along the mRNA during protein synthesis
J. Biol. Chem.
(1994)Hfq: a bacterial Sm-like protein that mediates RNA–RNA interaction
Mol. Cell
(2002)The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs
Mol. Cell
(2002)
An antisense RNA inhibits translation by competing with standby ribosomes
Mol. Cell
Translational standby sites: how ribosomes may deal with the rapid folding kinetics of mRNA
J. Mol. Biol.
Unfolding of mRNA secondary structure by the bacterial translation initiation complex
Mol. Cell
Translational coupling at an intercistronic boundary of the Escherichia coli galactose operon
Cell
Conserved small non-coding RNAs that belong to the sigmaE regulon: role in down-regulation of outer membrane proteins
J. Mol. Biol.
Killer and protective ribosomes
Prog. Mol. Biol. Transl. Sci.
The seed region of a small RNA drives the controlled destruction of the target mRNA by the endoribonuclease RNase E
Mol. Cell
Structure and functions of ribosomal protein S1
Prog. Nucleic Acid Res. Mol. Biol.
Ribosome-messenger recognition in the absence of the Shine-Dalgarno interactions
FEBS Lett.
Ribosomal protein S1 is required for translation of most, if not all, natural mRNAs in Escherichia coli in vivo
J. Mol. Biol.
A unique mechanism regulating gene expression: translational inhibition by a complementary RNA transcript (micRNA)
Proc. Natl. Acad. Sci. U.S.A.
The small RNA RyhB activates the translation of shiA mRNA encoding a permease of shikimate, a compound involved in siderophore synthesis
Mol. Microbiol.
Two seemingly homologous noncoding RNAs act hierarchically to activate glmS mRNA translation
PLoS Biol.
DsrA RNA regulates translation of RpoS message by an anti-antisense mechanism, independent of its action as an antisilencer of transcription
Proc. Natl. Acad. Sci. U.S.A.
A trans-acting RNA as a control switch in Escherichia coli: DsrA modulates function by forming alternative structures
Proc. Natl. Acad. Sci. U.S.A.
Effect of RyhB small RNA on global iron use in Escherichia coli
J. Bacteriol.
Evidence for an autonomous 5′ target recognition domain in an Hfq-associated small RNA
Proc. Natl. Acad. Sci. U.S.A.
Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA
Mol. Microbiol.
Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?
Nat. Rev. Genet.
The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC
Nat. Struct. Mol. Biol.
The 3′-terminal sequence of Escherichia coli 16S ribosomal RNA: complementarity to nonsense triplets and ribosome binding sites
Proc. Natl. Acad. Sci. U.S.A.
Secondary structure of the ribosome binding site determines translational efficiency: a quantitative analysis
Proc. Natl. Acad. Sci. U.S.A.
Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression
Nature
Footprinting mRNA-ribosome complexes with chemical probes
EMBO J.
Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli
Genes Dev.
Small RNA-induced mRNA degradation achieved through both translation block and activated cleavage
Genes Dev.
RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs
Genes Dev.
Hfq binding at RhlB-recognition region of RNase E is crucial for the rapid degradation of target mRNAs mediated by sRNAs in Escherichia coli
Mol. Microbiol.
Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish
Science
Hfq is necessary for regulation by the untranslated RNA DsrA
J. Bacteriol.
Base-pairing requirement for RNA silencing by a bacterial small RNA and acceleration of duplex formation by Hfq
Mol. Microbiol.
Cited by (73)
The RNA-binding protein Hfq assembles into foci-like structures in nitrogen starved Escherichia coli
2020, Journal of Biological ChemistryPotential regulation of small RNAs on bacterial function activities in pig farm wastewater treatment plants
2020, Journal of Environmental Sciences (China)Citation Excerpt :In bacteria, non-coding RNAs of 50–500 nt in length are usually defined as small RNAs (sRNAs), which are mainly located in the intergenic region, and some are located in the 5′ and 3′ UTR regions of the coding gene (Tsai et al., 2015; Lei et al., 2019). Studies have shown that sRNAs play an important role in the function activities of bacteria such as bacterial transcriptional regulation, RNA processing and modification, mRNA stabilization, mRNA translation, protein degradation, plasmid replication, and bacterial infection (Caron et al., 2010; Desnoyers et al., 2013; Lei et al., 2019). However, most of the current research on bacterial sRNA was mainly carried out in specific laboratory conditions, such as known microbial species and specific media (Dong et al., 2018; Fu et al., 2018; Subramanian et al., 2018).
Hfq modulates global protein pattern and stress response in Bordetella pertussis
2020, Journal of ProteomicsCitation Excerpt :In the last decades it became evident that post-transcriptional regulation mediated by the RNA chaperone Hfq and non-coding RNAs plays a significant role in host-pathogen interactions. Bacterial non-coding RNAs modulate a wide range of bacterial physiological responses [1,2] and, in particular, the small regulatory RNAs (sRNAs) are central to post-transcriptional regulation as they base pair with the target mRNAs and modulate their stability and translation efficiency [3–6]. Hfq is a highly conserved bacterial post-transcriptional regulatory protein [7] that mediates and stabilizes the sRNA-mRNA interactions [8,9].
The bacterial endoribonuclease RNase E can cleave RNA in the absence of the RNA chaperone Hfq
2019, Journal of Biological ChemistryCitation Excerpt :This is analogous to the cognate binding of microRNA in eukaryotes (10, 24). Bacterial sRNAs usually repress translation of target mRNA by base-pairing with regions adjacent to or upstream of the ribosome-binding site, resulting in the blocking of ribosome entry and concomitant stimulation of the rapid decay of mRNA by a RNA degradosome (22, 25). Bacterial sRNA also positively regulate gene expression by pairing with mRNA; several sRNAs have been shown to activate the translation of the σ factor RpoS by relieving the inhibitory secondary structure of the rpoS mRNA leader form in the presence of the RNA chaperone Hfq protein (26).
Gene regulation for the extreme resistance to ionizing radiation of Deinococcus radiodurans
2019, GeneCitation Excerpt :Hundreds of sRNAs have been predicted to be present in E. coli, and approximately one hundred have been experimentally validated (Raghavan et al., 2011). To the best of our knowledge that is based on available results, most sRNAs interact with mRNA targets by an antisense mechanism, resulting in inhibition of translation via the blocking of ribosome binding to the Shine-Dalgarno sequence or mRNA degradation (Desnoyers et al., 2013). Broad distributions of sRNAs in three kingdoms of life and a considerable number sRNA species existing in each well-studied organism imply their important status in various cellular processes (Raghavan et al., 2011; Hinton et al., 2014; Baldrich et al., 2019).
On a stake-out: Mycobacterial small RNA identification and regulation
2019, Non-coding RNA Research
- *
Current address: Institut Atlantique de Recherche sur le Cancer, Pavillon Hôtel-Dieu, 35, rue Providence, Moncton, NB, E1C 8X3, Canada.