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  • Review Article
  • Published:

Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning

Nature Reviews Genetics volume 16, pages 517–529 (2015)Cite this article

Subjects

Key Points

  • Alternative genetic decoding can be either a global phenomenon that affects the decoding of most or all mRNAs, or a local recoding that affects particular sites in a few mRNAs.

  • Global alterations in the genetic code are usually caused by changes in the translation machinery.

  • Recoding is observed at specific mRNA locations and can be modulated by a variety of cis-elements and trans-factors.

  • Diverse recoding phenomena include the incorporation of non-standard amino acids, ribosomes that shift between reading frames or that bypass large untranslated gaps, and the trans-translation of two mRNA molecules for the synthesis of a single polypeptide.

  • Although only a small number of genes require recoding mechanisms for their expression, these genes probably occur in all organisms and are usually evolutionary conserved.

  • For genes that do not require altered decoding for expression, recoding may still have regulatory importance.

Abstract

The non-universality of the genetic code is now widely appreciated. Codes differ between organisms, and certain genes are known to alter the decoding rules in a site-specific manner. Recently discovered examples of decoding plasticity are particularly spectacular. These examples include organisms and organelles with disruptions of triplet continuity during the translation of many genes, viruses that alter the entire genetic code of their hosts and organisms that adjust their genetic code in response to changing environments. In this Review, we outline various modes of alternative genetic decoding and expand existing terminology to accommodate recently discovered manifestations of this seemingly sophisticated phenomenon.

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Figure 1: Freezing and melting of genetic decoding.
Figure 2: Components that shape alternative genetic decoding.
Figure 3: Relationship between nucleotide sequences and alternatively decoded proteins.

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Acknowledgements

This Review was inspired by the discussions during EMBO Workshop “Recoding: Reprogramming genetic decoding” that took place in Killarney, Ireland, on the 13–18 May 2014. Therefore, the authors are grateful to all participants who shared their ideas and experimental data during this meeting. They apologize to their colleagues whose relevant works were not cited as this article is not intended as a comprehensive review of the topic and the authors aimed to keep it concise. The authors wish to acknowledge support by SFI grants [12/IA/1335 to P.V.B. and 08/IN.I/B1889,12/IP/1492 to J.F.A], P.V.B. is also supported by Wellcome Trust grant [094423].

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Authors and Affiliations

  1. School of Biochemistry and Cell Biology, University College Cork, Ireland

    Pavel V. Baranov, John F. Atkins & Martina M. Yordanova

  2. Department of Human Genetics, University of Utah, 15 N 2030 E Rm. 7410, Salt Lake City, 84112–5330, Utah, USA

    John F. Atkins

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  1. Pavel V. Baranov
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Glossary

Genetic code

A correspondence between 64 triplet combinations of four nucleotides and their standard amino acid or stop meanings.

Variant genetic codes

Genetic codes that differ from the standard genetic code shown in Figure 1a.

Proteinogenic amino acids

Amino acids that are incorporated into proteins co-translationally.

Ribosomal frameshifting

A process in which a ribosome changes its reading frame.

Codon redefinition

A local change of codon meaning that is dependent on the context in which it occurs.

Translational bypassing

A process in which ribosomes skip three or more nucleotides without decoding.

Fixed codon reassignment

A complete unconditional change of the standard meaning of a codon.

Standard meaning

The way the translational machinery interprets a codon (coding for a proteinogenic amino acid or a signal for translation termination) unless it occurs in a specific context.

Codon capture

An evolutionary event in which a codon that disappears from a genome reappears in its descendant and acquires a different standard meaning, thus leading to a variant genetic code.

Ambiguous intermediate

An evolutionary state in the history of an organism evolving a variant genetic code in which a particular codon has two standard meanings.

Regulated codon reassignment

A conditional change of the standard meaning of a codon.

Recoding

A process of context- or condition-specific alteration of genetic decoding.

Stop codon readthrough

A redefinition of a stop codon to a sense codon irrespective of functional implications of the identity of the incorporated amino acid.

Proteoforms

Groups of sequence-related proteins arising from the same mRNA.

SECIS element

(Sec insertion sequence element). An mRNA secondary structure that functions as a stimulatory element for selenocysteine (Sec) incorporation.

Programmed ribosomal frameshifting

(PRF). Ribosomal frameshifting that is programmed (by a sequence context) to occur at a specific mRNA location.

Productive PRF

Programmed ribosomal frameshifting (PRF) that is required for the production of a functional protein product.

Abortive PRF

Programmed ribosomal frameshifting (PRF) that results in the synthesis of dysfunctional protein products or in the downregulation of functional protein synthesis.

Purifying evolutionary selection

The removal of disadvantageous traits. In the case of protein-coding sequences it results in a higher rate of synonymous substitutions relative to non-synonymous substitutions.

Frameshifting site

(Also known as frameshift site and shift site). A sequence in which ribosomal frameshifting takes place. It includes codons in the A- and P-sites of the ribosomes just before and after the frameshifting. It is useful to describe the sequence of the frameshifting site denoting codons in the original and new frames, for example, C.UU_A.GG_C. Such representation unambiguously reflects the direction (minus or plus) as well as the mechanism of frameshifting (+1, +2, and so on)

Stimulatory element

An mRNA element that is required for the efficient local alteration of genetic decoding.

P-site

The ribosomal site that accommodates the peptidyl-tRNA carrying the growing polypeptide chain.

Isoacceptor

One of a group of tRNA species carrying the same amino acids but with different anticodon sequences

A-site

The ribosomal site that accommodates either the aminoacyl-tRNA carrying the next amino acid to be added to the growing polypeptide chain or a release factor.

Byps

Non-coding gaps in mRNAs of mitochondria (in Magnusiomyces capitatus and related species) that escape decoding through frequent translational bypassing.

Trans-translation

A process in which a single protein is translated from two mRNA molecules as templates.

StopGo

(Also known as Stop-Carry on). A process in which the production of a polypeptide chain is interrupted at a specific place while triplet mRNA decoding continues. This results in the production of two protein products from a single open reading frame.

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Baranov, P., Atkins, J. & Yordanova, M. Augmented genetic decoding: global, local and temporal alterations of decoding processes and codon meaning. Nat Rev Genet 16, 517–529 (2015). https://doi.org/10.1038/nrg3963

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