Regulatory RNA


Beyond their coding capacity, RNA molecules serve structural, catalytic and regulatory functions. The latter are elicited by RNA–RNA interactions (antisense‐target), frequently resulting in complex three‐dimensional structures, and by RNA–protein interactions. The numerous examples known to date probably present only a first glimpse at this expanding field.

Keywords: antisense; plasmid; bacterial; stress response; virus‐associated

Figure 1.

Examples of antisense RNA inhibition mechanisms in plasmids. (a) Mechanisms used by plasmids related to ColE1. The antisense RNA binds to its target (pre‐primer) during transcription to induce a folding change that is incompatible with primer maturation. (b) A mechanism used by plasmids similar to R1, ColIbP9, and many others. Antisense RNA binds to a region within a rep mRNA and blocks translation. (c) The transcriptional attenuation mechanism of, for example, pIP501 and pT181. Antisense RNA binds to nascent rep mRNA to induce the formation of a terminator stem–loop.

Figure 2.

Experimentally determined or predicted secondary structures of regulatory RNAs. (a, b) Antisense RNAs that control copy numbers of plasmid R1 (a) and of plasmid ColE1 (b). (c) Antisense RNA of the hok/sok killer system of R1. (d) Antisense regulator of IS10 transposition. (e) Antisense regulator of conjugation of plasmid F. (f, g, h) Stress response regulators OxyS (f), MicF (g) and DsrA (h) from Escherichia coli. (i, j) Antisense RNAs controlling lysogeny in Salmonella typhimurium phage P22 Sar (i) and coliphages P1/P7 (j). (k, l, m) The short antisense RNA lin‐4 in its proposed complex with one of the lin‐14 target elements (grey letters; repeat 4) (k), and regulatory RNAs from adenovirus (l) and Epstein–Barr virus (m). The RNAs a–c and i are fully complementary to their target RNAs, RNA‐OUT (d) is fully complementary only in its 5′ half. Pink boxes indicate examples of known sites at which target binding initiates. Blue boxes show regions of target complementarity in ‘trans’‐encoded antisense RNAs. Only one of two such regions is shown for DsrA (h).

Figure 3.

Two examples of antisense‐target RNA binding pathways. (a) The proposed binding pathway of CopA to CopT, the target of plasmid R1. Binding initiates between loops on top of bulged stems, proceeds by helix extension (asymmetrically) and results in the major inhibitory complex (lower, left). The unidirectional broken arrow indicates that subsequent duplex formation is slow and biologically not important. (b) The binding pathway of Sok and hok mRNA. Here, binding initiates between the single‐stranded 5′ tail of Sok and a target stem–loop. A complicated binding intermediate (third structure from left) suffices for inhibition, but is converted to a full duplex.

Figure 4.

Models for different regulatory mechanisms used – the OxyS and DsrA cases. (a) Two proposed mechanisms for OxyS function. OxyS inhibition of fhlA translation is mediated by an antisense effect (upper), and OxyS repression of rpoS translation is due to binding of the translational activator Hfq. (b) Two antisense mechanisms proposed for DsrA: binding of DsrA to the hns mRNA blocks translation, and DsrA binding to an anti‐RBS segment of the rpoS mRNA activates translation.


Further Reading

Altuvia S, Zhang A, Argaman L, Tiwari A and Storz G (1998) The E. coli oxyS regulatory RNA represses fhlA translation by blocking ribosome binding. EMBO Journal 17: 6069–6075.

Bass BL (1997) RNA editing and hypermutation by adenosine deamination. Trends in Biochemical Sciences 22: 157–162.

Gerdes K, Gultyaev AP, Franch T, Pedersen K and Mikkelsen ND (1997) Antisense RNA‐regulated programmed cell death. Annual Review of Genetics 31: 1–31.

Hildebrandt M and Nellen W (1992) Differential antisense transcription from the Dictyostelium EB4 gene locus: implications on antisense‐mediated regulation of mRNA stability. Cell 69: 197–204.

Keiler KC, Waller PRH and Sauer RT (1996) Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNAs. Science 271: 990–993.

Oberstraß J and Nellen W (1997) Regulating genes with antisense RNA. In: Weiss Benjamin (ed.) Antisense Oligodeoxynucleotides and Antisense RNA, pp. 171–195. Boca Raton, FL: CRC Press.

Sharp TV, Schwemmle M, Jeffrey I et al. (1993) Comparative analysis of the regulation of the interferon‐inducible protein kinase PKR by Epstein‐Barr virus RNAs EBER‐1 and EBER‐2 and adenovirus VAI RNA. Nucleic Acids Research 21: 4483–4490.

Wagner EGH and Brantl S (1998) Kissing and RNA stability in antisense control of plasmid replication. Trends in Biochemical Sciences 23: 451–454.

Wagner EGH and Simons RW (1994) Antisense RNA control in bacteria, phage and plasmids. Annual Review of Microbiology 48: 713–742.

Wassarman KM, Zhang A and Storz G (1999) Small RNAs in Escherichia coli. Trends in Microbiology 7: 37–45.

Zeiler BN and Simons RW (1998) Antisense RNA structure and function. In: Simons Robert W and Grunberg‐Manago Marianne (eds) RNA Structure and Function, pp. 437–464. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.

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How to Cite close
Wagner, E Gerhart H, Altuvia, Shoshy, and Nellen, Wolfgang(Apr 2001) Regulatory RNA. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000886]