Regulation Outside the Box: New Mechanisms for Small RNAs

Overview

Journal Mol Microbiol

Specialties Microbiology
Molecular Biology

Date 2020 May 6

PMID 32367584

Citations 9

Authors

Kathrin S Frohlich

Kai Papenfort

Affiliations

Soon will be listed here.

Abstract

Regulation at the post-transcriptional level is an important mode of gene expression control in bacteria. Small RNA regulators (sRNAs) that act via intramolecular base-pairing with target mRNAs are key players in this process and most often sequester the target's ribosome binding site (RBS) to down-regulate translation initiation. Over the past few years, several exceptions from this mechanism have been reported, revealing that sRNAs are able to influence translation initiation from a distance. In this issue of Molecular Microbiology, Azam and Vanderpool show that repression of the manY mRNA by the sRNA SgrS relies on an unconventional mechanism involving a translational enhancer element and ribosomal protein S1. Binding of S1 to an AU-rich sequence within the 5' untranslated region of the manY transcript promotes translation of the mRNA, and base-pairing of SgrS to the same site can interfere with this process. Therefore, instead of blocking translation initiation by occluding the manY RBS, SgrS reduces ManY synthesis by inhibiting S1-dependent translation activation. These findings increase the base-pairing window for sRNA-mediated gene expression control in bacteria and highlight the role of ribosomal protein S1 for translation initiation.

Citing Articles

An sRNA overexpression library reveals AbnZ as a negative regulator of an essential translocation module in Caulobacter crescentus.

Velasco-Gomariz M, Sulzer J, Faber F, Frohlich K Nucleic Acids Res. 2024; 53(1.

PMID: 39657128 PMC: 11724286. DOI: 10.1093/nar/gkae1139.

The pathogenicity island 1-encoded small RNA InvR mediates post-transcriptional feedback control of the activator HilA in .

Hou Y, Kim K, Cakar F, Golubeva Y, Slauch J, Vanderpool C bioRxiv. 2024; .

PMID: 39605656 PMC: 11601589. DOI: 10.1101/2024.11.21.624761.

RIL-seq reveals extensive involvement of small RNAs in virulence and capsule regulation in hypervirulent Klebsiella pneumoniae.

Goh K, Altuvia Y, Argaman L, Raz Y, Bar A, Lithgow T Nucleic Acids Res. 2024; 52(15):9119-9138.

PMID: 38804271 PMC: 11347178. DOI: 10.1093/nar/gkae440.

Global Hfq-mediated RNA interactome of nitrogen starved Escherichia coli uncovers a conserved post-transcriptional regulatory axis required for optimal growth recovery.

McQuail J, Matera G, Grafenhan T, Bischler T, Haberkant P, Stein F Nucleic Acids Res. 2023; 52(5):2323-2339.

PMID: 38142457 PMC: 10954441. DOI: 10.1093/nar/gkad1211.

Understanding the Effect of Different Glucose Concentrations in the Oligotrophic Bacterium BS-G1 through Transcriptomics Analysis.

Chen L, Wang C, Su J Microorganisms. 2023; 11(10).

PMID: 37894061 PMC: 10609351. DOI: 10.3390/microorganisms11102401.

References

Takahashi S, Furusawa H, Ueda T, Okahata Y . Translation enhancer improves the ribosome liberation from translation initiation. J Am Chem Soc. 2013; 135(35):13096-106. DOI: 10.1021/ja405967h. View

Jagodnik J, Chiaruttini C, Guillier M . Stem-Loop Structures within mRNA Coding Sequences Activate Translation Initiation and Mediate Control by Small Regulatory RNAs. Mol Cell. 2017; 68(1):158-170.e3. DOI: 10.1016/j.molcel.2017.08.015. View

Papenfort K, Bouvier M, Mika F, Sharma C, Vogel J . Evidence for an autonomous 5' target recognition domain in an Hfq-associated small RNA. Proc Natl Acad Sci U S A. 2010; 107(47):20435-40. PMC: 2996696. DOI: 10.1073/pnas.1009784107. View

Hor J, Gorski S, Vogel J . Bacterial RNA Biology on a Genome Scale. Mol Cell. 2018; 70(5):785-799. DOI: 10.1016/j.molcel.2017.12.023. View

Desnoyers G, Masse E . Noncanonical repression of translation initiation through small RNA recruitment of the RNA chaperone Hfq. Genes Dev. 2012; 26(7):726-39. PMC: 3323883. DOI: 10.1101/gad.182493.111. View

Frohlich K, Papenfort K . Regulation outside the box: New mechanisms for small RNAs. Mol Microbiol. 2020; 114(3):363-366. PMC: 7534054. DOI: 10.1111/mmi.14523. View

Cifuentes-Goches J, Hernandez-Ancheyta L, Guarneros G, Oviedo N, Hernandez-Sanchez J . Domains two and three of Escherichia coli ribosomal S1 protein confers 30S subunits a high affinity for downstream A/U-rich mRNAs. J Biochem. 2019; 166(1):29-40. DOI: 10.1093/jb/mvz006. View

Sharma C, Darfeuille F, Plantinga T, Vogel J . A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. Genes Dev. 2007; 21(21):2804-17. PMC: 2045133. DOI: 10.1101/gad.447207. View

Romilly C, Deindl S, Wagner E . The ribosomal protein S1-dependent standby site in mRNA consists of a single-stranded region and a 5' structure element. Proc Natl Acad Sci U S A. 2019; 116(32):15901-15906. PMC: 6690012. DOI: 10.1073/pnas.1904309116. View

10.

Unoson C, Wagner E . Dealing with stable structures at ribosome binding sites: bacterial translation and ribosome standby. RNA Biol. 2007; 4(3):113-7. DOI: 10.4161/rna.4.3.5350. View

11.

Orr M, Mao Y, Storz G, Qian S . Alternative ORFs and small ORFs: shedding light on the dark proteome. Nucleic Acids Res. 2019; 48(3):1029-1042. PMC: 7026640. DOI: 10.1093/nar/gkz734. View

12.

Meydan S, Marks J, Klepacki D, Sharma V, Baranov P, Firth A . Retapamulin-Assisted Ribosome Profiling Reveals the Alternative Bacterial Proteome. Mol Cell. 2019; 74(3):481-493.e6. PMC: 7115971. DOI: 10.1016/j.molcel.2019.02.017. View

13.

Azam M, Vanderpool C . Translational regulation by bacterial small RNAs via an unusual Hfq-dependent mechanism. Nucleic Acids Res. 2018; 46(5):2585-2599. PMC: 5861419. DOI: 10.1093/nar/gkx1286. View

14.

Tree J, Granneman S, McAteer S, Tollervey D, Gally D . Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli. Mol Cell. 2014; 55(2):199-213. PMC: 4104026. DOI: 10.1016/j.molcel.2014.05.006. View

15.

Frohlich K, Forstner K, Gitai Z . Post-transcriptional gene regulation by an Hfq-independent small RNA in Caulobacter crescentus. Nucleic Acids Res. 2018; 46(20):10969-10982. PMC: 6237742. DOI: 10.1093/nar/gky765. View

16.

Frohlich K, Papenfort K, Berger A, Vogel J . A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD. Nucleic Acids Res. 2011; 40(8):3623-40. PMC: 3333887. DOI: 10.1093/nar/gkr1156. View

17.

Woodson S, Panja S, Santiago-Frangos A . Proteins That Chaperone RNA Regulation. Microbiol Spectr. 2018; 6(4). PMC: 6086601. DOI: 10.1128/microbiolspec.RWR-0026-2018. View

18.

Papenfort K, Vanderpool C . Target activation by regulatory RNAs in bacteria. FEMS Microbiol Rev. 2015; 39(3):362-78. PMC: 4542691. DOI: 10.1093/femsre/fuv016. View

19.

Takyar S, Hickerson R, Noller H . mRNA helicase activity of the ribosome. Cell. 2005; 120(1):49-58. DOI: 10.1016/j.cell.2004.11.042. View

20.

Wagner E . Cycling of RNAs on Hfq. RNA Biol. 2013; 10(4):619-26. PMC: 3710369. DOI: 10.4161/rna.24044. View