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  • Review Article
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Ribozymes, riboswitches and beyond: regulation of gene expression without proteins

Nature Reviews Genetics volume 8, pages 776–790 (2007)Cite this article

Key Points

  • Modern organisms contain many protein-devoid RNA elements which have important roles in various cellular processes.

  • The collection of cleaving and splicing ribozymes has been recently supplemented by several eukaryotic and prokaryotic genome-encoded ribozymes that are present in pre-mRNA and mRNA molecules. These ribozymes seem to be involved in gene expression control and possibly in other basic cellular functions.

  • Other RNA-based elements and molecules, such as thermosensors, sRNAs, riboswitches and other RNA switches, can sense or react to changes in the environment and regulate gene expression through various mechanisms, including transcriptional, translational and splicing control.

  • The three-dimensional structures of ribozymes and riboswitches share several architectural principals. Given this commonality, some of these RNA molecules show striking similarities in molecular recognition and mechanistic aspects of their function.

  • RNA-based elements are probably more versatile than previously thought: they show some features that are typical of proteins and, in some situations, they might have functional advantages over proteins. For example, riboswitches can directly sense the concentration of cellular metabolites and control gene expression without a requirement for proteins, conserving cellular resources and providing fine control of gene expression.

  • Although the origins and evolution of RNA-based elements are not clear, some of these RNAs might have descended from a hypothetical primordial 'RNA world'.

Abstract

Although various functions of RNA are carried out in conjunction with proteins, some catalytic RNAs, or ribozymes, which contribute to a range of cellular processes, require little or no assistance from proteins. Furthermore, the discovery of metabolite-sensing riboswitches and other types of RNA sensors has revealed RNA-based mechanisms that cells use to regulate gene expression in response to internal and external changes. Structural studies have shown how these RNAs can carry out a range of functions. In addition, the contribution of ribozymes and riboswitches to gene expression is being revealed as far more widespread than was previously appreciated. These findings have implications for understanding how cellular functions might have evolved from RNA-based origins.

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Figure 1: Domain organization and secondary and three-dimensional structures of ribozymes.
Figure 2: Reactions catalysed by ribozymes.
Figure 3: Gene regulation by RNA switches.
Figure 4: Secondary and tertiary structures of riboswitches.

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Acknowledgements

This work was supported by the US National Institutes of Health grant GM073618.

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Authors and Affiliations

  1. Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, 10021, New York, USA

    Alexander Serganov & Dinshaw J. Patel

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  1. Alexander Serganov
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Correspondence to Alexander Serganov or Dinshaw J. Patel.

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DATABASES

Protein Data Bank Identification (PDB ID)

Asoarcus spp. BH72 group I intron

Bacillus antracis glmS ribozyme

Bacillus subtilis RNase P, B-type

Bacillus subtilis xpt gene

Escherichia coli thiM

Hairpin ribozyme

Hammerhead ribozyme

Hepatitis δ virus ribozyme

Thermoanaerobacter tengcongensis riboswitch

FURTHER INFORMATION

Dinshaw J. Patel's homepage

Glossary

Satellite RNAs

Subviral agents whose multiplication in a host cell depends on coinfection with a helper virus.

Rolling-circle replication

A process of replication of some circular genomes, whereby one strand is replicated first and the second strand is replicated after completion of the first one.

RNA maturase

A protein enzyme, intron-specific, that acts as a cofactor to facilitate splicing.

Homing endonucleases

dsDNA-specific deoxyribonucleases that recognize large asymmetrical DNA sequences, which are not stringently defined, and which mobilize these DNA elements by facilitating their integration into new genomic sites. Because these sites lack introns and inteins (protein introns), this form of mobility is termed 'homing'. Homing endonucleases are encoded by intervening sequences embedded in either introns or inteins.

Reverse transcriptase

An RNA-dependent DNA polymerase that transcribes ssRNA into dsDNA.

Transcriptional attenuation

A regulatory mechanism whereby gene expression is controlled through the formation of alternative structures in the mRNA sequence that inhibit or facilitate the progression of transcription.

Aptamer

Derived from the Latin aptus, meaning 'to fit', aptamers are oligonucleotide or peptide molecules that bind specific target molecules. The term is usually applied to nucleic acid molecules that are created following selection from a large random sequence pool, as well as to natural metabolite-sensing domains in riboswitches, which possess similar recognition properties to artificially generated aptamers.

Boolean NOR logic gate

Boolean logic, named after George Boole, is a complete system for logical operations. A logic gate performs a logical operation on one or more logical inputs and produces a single logical output. The logical NOR, or joint denial, is a logical operator, meaning that the output is true if none of the inputs are true. Consequently, if one or both inputs are true, then the output is not true.

Prosthetic group

A non-protein component of a conjugated protein that is usually essential for the protein's function. Prosthetic groups are also called coenzymes and cofactors.

Lateral transfer

A process of transferring genetic material from one organism to another without reproduction. Also called horizontal gene transfer.

Telomerase

An RNA-containing reverse transcriptase that adds DNA sequence repeats (telomeric repeats) to the 3′ end of DNA strands in eukaryotic chromosomes using its RNA component as a synthesis template.

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Serganov, A., Patel, D. Ribozymes, riboswitches and beyond: regulation of gene expression without proteins. Nat Rev Genet 8, 776–790 (2007). https://doi.org/10.1038/nrg2172

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