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  • Review Article
  • Published:

Termination and antitermination: RNA polymerase runs a stop sign

Nature Reviews Microbiology volume 9, pages 319–329 (2011)Cite this article

Subjects

Key Points

  • The transcription elongation complex is composed of a multisubunit RNA polymerase (RNAP), a DNA template and a nascent RNA. This complex is normally extremely stable but can be efficiently disassembled by the action of select proteins, called termination factors, or specific sequences, called intrinsic terminators.Regulated transcription termination is the underlying mechanism of attenuation, riboswitch function and polar repression of downstream expression. Efficient termination is also necessary to halt transcription elongation complexes at the end of genes in order to block unproductive or aberrant expression of downstream genes.Expression of many genes, most notably those encoding ribosomal RNA, is critically dependent on antitermination mechanisms that modify RNAP into a termination-resistant state.

  • Antitermination factors can modulate or block the activity of termination factors, override intrinsic terminators in leader sequences under conditions necessitating downstream expression, and modify the activity of RNAP to provide expression of select genes (for example, upon phage infection).

  • Many antitermination factors act just once during mRNA synthesis by blocking the formation of an RNA hairpin structure that is necessary for intrinsic termination. These factors usually employ direct binding to RNA, and structures as large as translating ribosomes are used to determine the RNA fold.

  • Processive antitermination factors bind to, and modify the activity of, elongating RNAP such that the modified complex is resistant to multiple or tandem downstream termination signals. Studies of antitermination factors provide important insights into mechanisms of processive RNA synthesis in all domains. These factors provide stability to the transcription complex, either by shielding the encapsulated nucleic acids or preventing structural changes in RNAP necessary for RNA release and complex disassembly.

Abstract

Termination signals induce rapid and irreversible dissociation of the nascent transcript from RNA polymerase. Terminators at the end of genes prevent unintended transcription into the downstream genes, whereas terminators in the upstream regulatory leader regions adjust expression of the structural genes in response to metabolic and environmental signals. Premature termination within an operon leads to potentially deleterious defects in the expression of the downstream genes, but also provides an important surveillance mechanism. This Review discusses the actions of bacterial and phage antiterminators that allow RNA polymerase to override a terminator when the circumstances demand it.

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Figure 1: Schematic model of the elongation complex.
Figure 2: Bacterial termination signals.
Figure 3: Differential folding of a nascent RNA.
Figure 4: A model for termination and antitermination.
Figure 5: Processive antitermination mechanisms.
Figure 6: Targets for processive antiterminators.

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Acknowledgements

We thank N. Ruiz and the anonymous referees for their help in improving the manuscript. This work was supported by the US National Institutes of Health grants GM67153 (to I.A.) and F32-GM073336 (to T.J.S.).

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  1. Department of Microbiology and The RNA Group, The Ohio State University, Columbus, 43210, Ohio, USA

    Thomas J. Santangelo & Irina Artsimovitch

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  1. Thomas J. Santangelo
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  2. Irina Artsimovitch
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Correspondence to Irina Artsimovitch.

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Glossary

Pause site

A signal that causes the elongation complex to stall temporarily.

Arrest site

A signal at which the elongation complex comes to a complete halt but does not dissociate.

Polarity

A quality control mechanism in which Rho terminates the transcription of mRNAs that are not translated.

R-loops

DNA loops behind RNA polymerase that are created when the nascent RNA invades the DNA duplex and pairs with the template DNA strand.

rrn operons

The operons that contain ribosomal RNA and tRNA genes.

Leader regions

Regions of DNA that separate promoters from structural genes. Leaders play diverse regulatory roles as riboswitches, attenuators and targets for auxiliary factors.

RF2

Release factor 2. A release factor that mediates hydrolysis of the peptidyl-tRNA ester bond at UAA and UGA stop codons.

Zinc-finger

A small protein motif in which the structure is stabilized by a bound Zn2+ ion.

Transcription bubble

A 12–14-nucleotide region in which the template and the non-template DNA strands are separated by the RNA polymerase.

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Santangelo, T., Artsimovitch, I. Termination and antitermination: RNA polymerase runs a stop sign. Nat Rev Microbiol 9, 319–329 (2011). https://doi.org/10.1038/nrmicro2560

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