Chapter 31 : Synthetic Biology of Small RNAs and Riboswitches

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RNAs have been known to perform a vast amount of regulatory functions in bacteria and archaea. Small RNAs (sRNAs) and riboswitches are two extensively studied classes of regulatory RNAs. sRNAs are -acting RNA elements between ∼50 and 500 nucleotides (nt) in length that are either independently transcribed or processed from a nontarget mRNA, and contain imperfect complementarity to the target mRNA to perform posttranscriptional regulatory functions. On the contrary, riboswitches are -regulatory structured RNA elements in the untranslated regions of mRNAs, capable of regulating downstream gene expression through small-molecule ligand-induced conformational switching. These regulatory RNAs have revealed the precise and sophisticated nature of natural gene regulatory networks and have inspired efforts to mimic these mechanisms and functions by engineering RNA tools for an increasing number of synthetic biology applications.

Citation: Villa* J, Su* Y, Contreras L, Hammond M. 2019. Synthetic Biology of Small RNAs and Riboswitches, p 527-545. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0007-2017
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Figure 1

Timeline of sRNA and riboswitch discovery, including relevant technological advances that aided identification and verification of regulatory RNAs. The development of high-throughput, deep-sequencing techniques in particular has led to an explosion of sRNA and riboswitch discovery. However, although identification of sRNAs and riboswitches has rapidly expanded, verification of function still lags behind.

Citation: Villa* J, Su* Y, Contreras L, Hammond M. 2019. Synthetic Biology of Small RNAs and Riboswitches, p 527-545. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0007-2017
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Figure 2

General function of sRNAs (A to D) and riboswitches (a to f). sRNAs regulate gene expression in through several functions enacted by antisense interactions, including transcription attenuation/enhancement through interactions with the RNA polymerase (A), inhibition of protein or ribosome binding either indirectly (B) or directly (C), and sequestration of protein factors (such as CsrA) (D). Riboswitches regulate gene expression in through a ligand-induced conformational change in the expression platform. The resulting gene expression consequences include Rho-dependent/independent transcription termination (a, b), transcription antitermination (c), translation activation (d), translation inhibition (e), and mRNA degradation (f).

Citation: Villa* J, Su* Y, Contreras L, Hammond M. 2019. Synthetic Biology of Small RNAs and Riboswitches, p 527-545. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0007-2017
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Figure 3

Examples of applications of sRNAs and riboswitches. Applications of these regulatory RNAs are rooted in their unique functional characteristics (antisense interactions for sRNA and ligand binding for riboswitches). Recent applications of these systems have begun to interweave these mechanisms to provide more complex engineering strategies.

Citation: Villa* J, Su* Y, Contreras L, Hammond M. 2019. Synthetic Biology of Small RNAs and Riboswitches, p 527-545. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0007-2017
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Table 1

General considerations for synthetic design: comparison of general factors to be considered in synthetic applications of small regulatory RNAs and riboswitches

Citation: Villa* J, Su* Y, Contreras L, Hammond M. 2019. Synthetic Biology of Small RNAs and Riboswitches, p 527-545. In Storz G, Papenfort K (ed), Regulating with RNA in Bacteria and Archaea. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.RWR-0007-2017

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