Chapter 25 : Sponges and Predators in the Small RNA World

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Sponges and Predators in the Small RNA World, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781683670247/9781683670230_Chap25-1.gif /docserver/preview/fulltext/10.1128/9781683670247/9781683670230_Chap25-2.gif


MicroRNAs (miRNAs) are 20- to-24-nucleotide (nt)-long RNAs that guide Argonaute proteins to silence mRNA expression in animal and plant cells ( ). Similarly to bacterial -encoded small RNAs (sRNAs), miRNAs act by establishing imperfect base-pair interactions with seed sequences that can be as short as 6 to 8 nt. Seeking ways to selectively control miRNA activity , a decade ago Ebert and coworkers engineered transcripts containing multiple tandemly arranged target sites for one or more miRNAs and had these constructs expressed at high levels in transfected mammalian cells ( ). They found the exogenous RNAs to have the ability to sequester (“soak up”) the miRNAs, relieving the regulation of their natural targets. The authors termed the artificial transcripts “microRNA sponges.” At about the same time, a study on the mechanism responsible for inhibiting the activity of a miRNA (miR399) in plant cells identified an endogenous noncoding RNA, named IPS1, that could base-pair with miR399 and compete for its binding to the primary target ( ). This indicated that a natural RNA could have sponge-like activity and that target site amplification was not required for this effect. Following these initial findings, several examples of miRNA target mimicry have been described involving different types of coding and noncoding RNAs ( ), including some of viral origin ( ). Particularly noteworthy is the case of the circular antisense RNA named CDR1as, highly expressed in human and mouse brain, which harbors as many as 74 potential target sites for the miR-7 miRNA and thus closely fulfills the original definition of a sponge ( ). Recent evidence showed CDR1as to be a highly efficient miR-7 sponge : in cells lacking CDR1as, deregulation of miR-7 networks leads to profound defects in brain development and function ( ).

Citation: Figueroa-Bossi N, Bossi L. 2019. Sponges and Predators in the Small RNA World, p 441-451. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0021-2018
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1
Figure 1

Regulation of chitosugar uptake in and . The gene and the operon encode proteins involved in the uptake and utilization of chitin-derived sugars. When no chitosugars are available, ChiP synthesis is prevented by constitutively made ChiX sRNA, which represses translation of mRNA (made at a relatively high basal level), while the operon is repressed transcriptionally by the NagC repressor (not shown). ChiX further lowers the uninduced levels of the mRNA by pairing with a sequence in the intercistronic region. In the presence of chitosugars, transcriptional activation of operon produces a large accumulation of the polycistronic mRNA. Now in excess over ChiX, this mRNA titrates out ChiX through base-pairing and promotes its degradation. ChiX depletion results in the derepression of the mRNA.

Citation: Figueroa-Bossi N, Bossi L. 2019. Sponges and Predators in the Small RNA World, p 441-451. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0021-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

sRNA sponging by a tRNA spacer sequence. The sRNAs RybB (blue) and RyhB (purple) are made in response to envelope stress or iron limitation, respectively. An ∼50-nt RNA, named 3′ETS (red), released by RNase E cleavage of the tRNA precursor (top) can form stable base-pair interactions with both RybB and RyhB. This allows 3′ETS to capture and sequester RybB and RyhB molecules that are made adventitiously (in the absence of any stress) due to transcriptional noise (left). Under inducing conditions (envelope stress or iron limitation), accumulation of either RybB or RyhB saturates the sponging capacity of 3′ETS. This sets the threshold concentration (dotted line) that either of the two sRNAs must attain to begin performing its regulatory task: downregulation of OMPs for RybB (middle) or of nonessential iron-binding proteins for RyhB (right).

Citation: Figueroa-Bossi N, Bossi L. 2019. Sponges and Predators in the Small RNA World, p 441-451. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0021-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3
Figure 3

Target-mediated derepression of the GcvB regulon. The sRNA GcvB downregulates several mRNAs encoding amino acid and small peptide transporters. Among these is the mRNA (left). Presence of a leaky Rho-independent transcription terminator in the spacer between and causes a fraction of transcripts initiating at the promoter to terminate prematurely in the spacer region (right). RNase E cleavage of the prematurely terminated transcripts generates SroC, an ∼150-nt RNA, which captures GcvB through a base-pairing interaction and destabilizes it. As a result, all of the GcvB targets become derepressed. Since the SroC precursor RNA itself is one of these targets, SroC activity drives a feedforward regulatory loop.

Citation: Figueroa-Bossi N, Bossi L. 2019. Sponges and Predators in the Small RNA World, p 441-451. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0021-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

A sponging relay model. Depicted are two hypothetical sRNA networks (A and B) linked by an mRNA node (cyan-filled circle). (Top) The two sRNAs downregulate their respective targets. (Bottom) A transcriptional regulatory event leads to a large increase in the concentration of one of the mRNAs in network A (yellow-filled circle). The accumulated mRNA sequesters and destabilizes its cognate sRNA, resulting in the derepression of the entire network A, including the nodal mRNA. In turn, the latter acts as a sponge for cognate sRNA in network B, thus relieving, or attenuating (depicted here), the repression of the B network.

Citation: Figueroa-Bossi N, Bossi L. 2019. Sponges and Predators in the Small RNA World, p 441-451. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0021-2018
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Ambros V . 2004. The functions of animal microRNAs. Nature 431 : 350 355.[CrossRef][PubMed]
2. Bartel DP . 2009. MicroRNAs: target recognition and regulatory functions. Cell 136 : 215 233.[CrossRef][PubMed]
3. Jones-Rhoades MW,, Bartel DP,, Bartel B . 2006. MicroRNAS and their regulatory roles in plants. Annu Rev Plant Biol 57 : 19 53.[CrossRef][PubMed]
4. Ebert MS,, Neilson JR,, Sharp PA . 2007. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4 : 721 726.[CrossRef][PubMed]
5. Franco-Zorrilla JM,, Valli A,, Todesco M,, Mateos I,, Puga MI,, Rubio-Somoza I,, Leyva A,, Weigel D,, García JA,, Paz-Ares J . 2007. Target mimicry provides a new mechanism for regulation of microRNA activity. Nat Genet 39 : 1033 1037.[CrossRef][PubMed]
6. Cesana M,, Cacchiarelli D,, Legnini I,, Santini T,, Sthandier O,, Chinappi M,, Tramontano A,, Bozzoni I . 2011. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147 : 358 369.[CrossRef][PubMed]
7. Hansen TB,, Jensen TI,, Clausen BH,, Bramsen JB,, Finsen B,, Damgaard CK,, Kjems J . 2013. Natural RNA circles function as efficient microRNA sponges. Nature 495 : 384 388.[CrossRef][PubMed]
8. Marcinowski L,, Tanguy M,, Krmpotic A,, Rädle B,, Lisnić VJ,, Tuddenham L,, Chane-Woon-Ming B,, Ruzsics Z,, Erhard F,, Benkartek C,, Babic M,, Zimmer R,, Trgovcich J,, Koszinowski UH,, Jonjic S,, Pfeffer S,, Dölken L . 2012. Degradation of cellular mir-27 by a novel, highly abundant viral transcript is important for efficient virus replication in vivo. PLoS Pathog 8 : e1002510.[CrossRef][PubMed]
9. Cazalla D,, Yario T,, Steitz JA . 2010. Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science 328 : 1563 1566.[CrossRef][PubMed]
10. Memczak S,, Jens M,, Elefsinioti A,, Torti F,, Krueger J,, Rybak A,, Maier L,, Mackowiak SD,, Gregersen LH,, Munschauer M,, Loewer A,, Ziebold U,, Landthaler M,, Kocks C,, le Noble F,, Rajewsky N . 2013. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495 : 333 338.[CrossRef][PubMed]
11. Piwecka M,, Glažar P,, Hernandez-Miranda LR,, Memczak S,, Wolf SA,, Rybak-Wolf A,, Filipchyk A,, Klironomos F,, Cerda Jara CA,, Fenske P,, Trimbuch T,, Zywitza V,, Plass M,, Schreyer L,, Ayoub S,, Kocks C,, Kühn R,, Rosenmund C,, Birchmeier C,, Rajewsky N . 2017. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science 357 : eaam8526.[CrossRef][PubMed]
12. Seitz H . 2009. Redefining microRNA targets. Curr Biol 19 : 870 873.[CrossRef][PubMed]
13. Salmena L,, Poliseno L,, Tay Y,, Kats L,, Pandolfi PP . 2011. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146 : 353 358.[CrossRef][PubMed]
14. Denzler R,, Agarwal V,, Stefano J,, Bartel DP,, Stoffel M . 2014. Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance. Mol Cell 54 : 766 776.[CrossRef][PubMed]
15. Denzler R,, McGeary SE,, Title AC,, Agarwal V,, Bartel DP,, Stoffel M . 2016. Impact of microRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression. Mol Cell 64 : 565 579.[CrossRef][PubMed]
16. Jens M,, Rajewsky N . 2015. Competition between target sites of regulators shapes post-transcriptional gene regulation. Nat Rev Genet 16 : 113 126.[CrossRef][PubMed]
17. Figliuzzi M,, Marinari E,, De Martino A . 2013. MicroRNAs as a selective channel of communication between competing RNAs: a steady-state theory. Biophys J 104 : 1203 1213.[CrossRef][PubMed]
18. Gottesman S,, Storz G . 2011. Bacterial small RNA regulators: versatile roles and rapidly evolving variations. Cold Spring Harb Perspect Biol 3 : a003798.[CrossRef][PubMed]
19. Storz G,, Vogel J,, Wassarman KM . 2011. Regulation by small RNAs in bacteria: expanding frontiers. Mol Cell 43 : 880 891.[CrossRef][PubMed]
20. Wagner EG,, Romby P . 2015. Small RNAs in bacteria and archaea: who they are, what they do, and how they do it. Adv Genet 90 : 133 208.[CrossRef][PubMed]
21. Levine E,, Zhang Z,, Kuhlman T,, Hwa T . 2007. Quantitative characteristics of gene regulation by small RNA. PLoS Biol 5 : e229.[CrossRef][PubMed]
22. Overgaard M,, Johansen J,, Møller-Jensen J,, Valentin-Hansen P . 2009. Switching off small RNA regulation with trap-mRNA. Mol Microbiol 73 : 790 800.[CrossRef][PubMed]
23. Bossi L,, Figueroa-Bossi N . 2016. Competing endogenous RNAs: a target-centric view of small RNA regulation in bacteria. Nat Rev Microbiol 14 : 775 784.[CrossRef][PubMed]
24. Figueroa-Bossi N,, Valentini M,, Malleret L,, Fiorini F,, Bossi L . 2009. Caught at its own game: regulatory small RNA inactivated by an inducible transcript mimicking its target. Genes Dev 23 : 2004 2015.[CrossRef][PubMed]
25. Plumbridge J,, Pellegrini O . 2004. Expression of the chitobiose operon of Escherichia coli is regulated by three transcription factors: NagC, ChbR and CAP. Mol Microbiol 52 : 437 449.[CrossRef][PubMed]
26. Plumbridge J,, Bossi L,, Oberto J,, Wade JT,, Figueroa-Bossi N . 2014. Interplay of transcriptional and small RNA-dependent control mechanisms regulates chitosugar uptake in Escherichia coli and Salmonella. Mol Microbiol 92 : 648 658.[CrossRef][PubMed]
27. Johansen J,, Rasmussen AA,, Overgaard M,, Valentin-Hansen P . 2006. Conserved small non-coding RNAs that belong to the σ E regulon: role in down-regulation of outer membrane proteins. J Mol Biol 364 : 1 8.[CrossRef][PubMed]
28. Papenfort K,, Pfeiffer V,, Mika F,, Lucchini S,, Hinton JC,, Vogel J . 2006. σ E-dependent small RNAs of Salmonella respond to membrane stress by accelerating global omp mRNA decay. Mol Microbiol 62 : 1674 1688.[CrossRef][PubMed]
29. Massé E,, Vanderpool CK,, Gottesman S . 2005. Effect of RyhB small RNA on global iron use in Escherichia coli. J Bacteriol 187 : 6962 6971.[CrossRef][PubMed]
30. Jacques JF,, Jang S,, Prévost K,, Desnoyers G,, Desmarais M,, Imlay J,, Massé E . 2006. RyhB small RNA modulates the free intracellular iron pool and is essential for normal growth during iron limitation in Escherichia coli. Mol Microbiol 62 : 1181 1190.[CrossRef][PubMed]
31. Lalaouna D,, Carrier MC,, Semsey S,, Brouard JS,, Wang J,, Wade JT,, Massé E . 2015. A 3′ external transcribed spacer in a tRNA transcript acts as a sponge for small RNAs to prevent transcriptional noise. Mol Cell 58 : 393 405.[CrossRef][PubMed]
32. Costanzo A,, Nicoloff H,, Barchinger SE,, Banta AB,, Gourse RL,, Ades SE . 2008. ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor σ E in Escherichia coli by both direct and indirect mechanisms. Mol Microbiol 67 : 619 632.[CrossRef][PubMed]
33. Gopalkrishnan S,, Nicoloff H,, Ades SE . 2014. Co-ordinated regulation of the extracytoplasmic stress factor, σ E, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes. Mol Microbiol 93 : 479 493.[CrossRef][PubMed]
34. Vinella D,, Albrecht C,, Cashel M,, D’Ari R . 2005. Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli. Mol Microbiol 56 : 958 970.[CrossRef][PubMed]
35. Sharma CM,, Darfeuille F,, Plantinga TH,, Vogel J . 2007. A small RNA regulates multiple ABC transporter mRNAs by targeting C/A-rich elements inside and upstream of ribosome-binding sites. Genes Dev 21 : 2804 2817.[CrossRef][PubMed]
36. Sharma CM,, Papenfort K,, Pernitzsch SR,, Mollenkopf HJ,, Hinton JC,, Vogel J . 2011. Pervasive post-transcriptional control of genes involved in amino acid metabolism by the Hfq-dependent GcvB small RNA. Mol Microbiol 81 : 1144 1165.[CrossRef][PubMed]
37. Urbanowski ML,, Stauffer LT,, Stauffer GV . 2000. The gcvB gene encodes a small untranslated RNA involved in expression of the dipeptide and oligopeptide transport systems in Escherichia coli. Mol Microbiol 37 : 856 868.[CrossRef][PubMed]
38. Stauffer GV, . 1996. Biosynthesis of serine, glycine and one carbon units, p 506 513. In Neidhardt FC,, Curtiss R III,, Ingraham JL,, Lin EC,, Low KB,, Magasanik B,, Reznikoff WS,, Riley M,, Schaechter M,, Umbarger HE (ed), Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd ed. ASM Press, Washington, DC.
39. Vogel J,, Bartels V,, Tang TH,, Churakov G,, Slagter-Jäger JG,, Hüttenhofer A,, Wagner EG . 2003. RNomics in Escherichia coli detects new sRNA species and indicates parallel transcriptional output in bacteria. Nucleic Acids Res 31 : 6435 6443.[CrossRef][PubMed]
40. Miyakoshi M,, Chao Y,, Vogel J . 2015. Cross talk between ABC transporter mRNAs via a target mRNA-derived sponge of the GcvB small RNA. EMBO J 34 : 1478 1492.[CrossRef][PubMed]
41. Morita T,, Ueda M,, Kubo K,, Aiba H . 2015. Insights into transcription termination of Hfq-binding sRNAs of Escherichia coli and characterization of readthrough products. RNA 21 : 1490 1501.[CrossRef][PubMed]
42. Moon K,, Gottesman S . 2009. A PhoQ/P-regulated small RNA regulates sensitivity of Escherichia coli to antimicrobial peptides. Mol Microbiol 74 : 1314 1330.[CrossRef][PubMed]
43. Acuña LG,, Barros MJ,, Peñaloza D,, Rodas PI,, Paredes-Sabja D,, Fuentes JA,, Gil F,, Calderón IL . 2016. A feed-forward loop between SroC and MgrR small RNAs modulates the expression of eptB and the susceptibility to polymyxin B in Salmonella Typhimurium. Microbiology 162 : 1996 2004.[CrossRef][PubMed]
44. Moon K,, Six DA,, Lee HJ,, Raetz CR,, Gottesman S . 2013. Complex transcriptional and post-transcriptional regulation of an enzyme for lipopolysaccharide modification. Mol Microbiol 89 : 52 64.[CrossRef][PubMed]
45. Tree JJ,, Granneman S,, McAteer SP,, Tollervey D,, Gally DL . 2014. Identification of bacteriophage-encoded anti-sRNAs in pathogenic Escherichia coli. Mol Cell 55 : 199 213.[CrossRef][PubMed]
46. Kudla G,, Granneman S,, Hahn D,, Beggs JD,, Tollervey D . 2011. Cross-linking, ligation, and sequencing of hybrids reveals RNA-RNA interactions in yeast. Proc Natl Acad Sci U S A 108 : 10010 10015.[CrossRef][PubMed]
47. Melamed S,, Peer A,, Faigenbaum-Romm R,, Gatt YE,, Reiss N,, Bar A,, Altuvia Y,, Argaman L,, Margalit H . 2016. Global mapping of small RNA-target interactions in bacteria. Mol Cell 63 : 884 897.[CrossRef][PubMed]
48. Hör J,, Vogel J . 2017. Global snapshots of bacterial RNA networks. EMBO J 36 : 245 247.[CrossRef][PubMed]
49. Waters SA,, McAteer SP,, Kudla G,, Pang I,, Deshpande NP,, Amos TG,, Leong KW,, Wilkins MR,, Strugnell R,, Gally DL,, Tollervey D,, Tree JJ . 2017. Small RNA interactome of pathogenic E. coli revealed through crosslinking of RNase E. EMBO J 36 : 374 387.[CrossRef][PubMed]
50. Mandin P,, Gottesman S . 2009. A genetic approach for finding small RNAs regulators of genes of interest identifies RybC as regulating the DpiA/DpiB two-component system. Mol Microbiol 72 : 551 565.[CrossRef][PubMed]
51. Beisel CL,, Storz G . 2011. The base-pairing RNA Spot 42 participates in a multioutput feedforward loop to help enact catabolite repression in Escherichia coli. Mol Cell 41 : 286 297.[CrossRef][PubMed]
52. Kröger C,, Colgan A,, Srikumar S,, Händler K,, Sivasankaran SK,, Hammarlöf DL,, Canals R,, Grissom JE,, Conway T,, Hokamp K,, Hinton JC . 2013. An infection-relevant transcriptomic compendium for Salmonella enterica serovar Typhimurium. Cell Host Microbe 14 : 683 695.[CrossRef][PubMed]
53. Mika F,, Busse S,, Possling A,, Berkholz J,, Tschowri N,, Sommerfeldt N,, Pruteanu M,, Hengge R . 2012. Targeting of csgD by the small regulatory RNA RprA links stationary phase, biofilm formation and cell envelope stress in Escherichia coli. Mol Microbiol 84 : 51 65.[CrossRef][PubMed]
54. Holmqvist E,, Reimegård J,, Sterk M,, Grantcharova N,, Römling U,, Wagner EG . 2010. Two antisense RNAs target the transcriptional regulator CsgD to inhibit curli synthesis. EMBO J 29 : 1840 1850.[CrossRef][PubMed]
55. Rutherford ST,, Bassler BL . 2012. Bacterial quorum sensing: its role in virulence and possibilities for its control. Cold Spring Harb Perspect Med 2 : a012427.[CrossRef][PubMed]
56. Feng L,, Rutherford ST,, Papenfort K,, Bagert JD,, van Kessel JC,, Tirrell DA,, Wingreen NS,, Bassler BL . 2015. A Qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics. Cell 160 : 228 240.[CrossRef][PubMed]
57. Beisel CL,, Storz G . 2010. Base pairing small RNAs and their roles in global regulatory networks. FEMS Microbiol Rev 34 : 866 882.[CrossRef][PubMed]
58. Nitzan M,, Rehani R,, Margalit H . 2017. Integration of bacterial small RNAs in regulatory networks. Annu Rev Biophys 46 : 131 148.[CrossRef][PubMed]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error