Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Atkins, John F.; Loughran, Gary; Bhatt, Pramod R.; Firth, Andrew E.; Baranov, Pavel V.

doi:10.1093/nar/gkw530

Cited by 239 publications

(337 citation statements)

References 817 publications

(1,125 reference statements)

Supporting

Mentioning

334

Contrasting

Unclassified

Order By: Relevance

“…While several cases of PRF are known in bacteria (Atkins et al, 2016), there is essentially only one well-substantiated example where -1 PRF leads to generation of two functional proteins from one gene ( dnaX ) (Blinkowa and Walker, 1990). Our finding that -1 PRF in the E. coli gene copA directs synthesis of two functional proteins illuminates a possible broader penetrance of this distinctive mechanism of protein coding and gene regulation.…”

Section: Discussionmentioning

confidence: 99%

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

et al. 2017

View full text Add to dashboard Cite

Summary Metal efflux pumps maintain ion homeostasis in the cell. The functions of the transporters are often supported by chaperone proteins, which scavenge the metal ions from the cytoplasm. Although the copper ion transporter CopA has been known in Escherichia coli, no gene for its chaperone had been identified. We show that the CopA chaperone is expressed in E. coli from the same gene that encodes the transporter. Some ribosomes translating copA undergo programmed frameshifting, terminate translation in the -1 frame, and generate the 70 amino acid-long polypeptide CopA(Z), which helps cells survive toxic copper concentrations. The high efficiency of frameshifting is achieved by the combined stimulatory action of a ‘slippery’ sequence, an mRNA pseudoknot, and the CopA nascent chain. Similar mRNA elements are not only found in the copA genes of other bacteria but are also present in ATP7B, the human homolog of copA, and direct ribosomal frameshifting in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Experiments to measure the fraction of ribosomes paused at this element, their pause times, and drop-off rates are planned for the future. A second set of insights stems from the observation that the CHIKV Ϫ1 PRF signal promotes relatively low rates of recoding (most viral frameshifting is in the range of Ն5%; see Atkins et al 37). Examination of sequences proximal to the Ϫ1 PRF signal did not reveal the potential to form either a larger stem-loop or a more complex structure, e.g.…”

Section: Chikungunya Virus Recoding Signalsmentioning

confidence: 99%

Functional and structural characterization of the chikungunya virus translational recoding signals

Kendra¹,

Advani

Chen³

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Climate change and human globalization have spurred the rapid spread of mosquito-borne diseases to naïve populations. One such emerging virus of public health concern is chikungunya virus (CHIKV), a member of the Togaviridae family, genus Alphavirus. CHIKV pathogenesis is predominately characterized by acute febrile symptoms and severe arthralgia, which can persist in the host long after viral clearance. CHIKV has also been implicated in cases of acute encephalomyelitis, and its vertical transmission has been reported. Currently, no FDA-approved treatments exist for this virus. Recoding elements help expand the coding capacity in many viruses and therefore represent potential therapeutic targets in antiviral treatments. Here, we report the molecular and structural characterization of two CHIKV translational recoding signals: a termination codon read-through (TCR) element located between the nonstructural protein 3 and 4 genes and a programmed ؊1 ribosomal frameshift (؊1 PRF) signal located toward the 3 end of the CHIKV 6K gene. Using Dual-Luciferase and immunoblot assays in HEK293T and U87MG mammalian cell lines, we validated and genetically characterized efficient TCR and ؊1 PRF. Analyses of RNA chemical modification data with selective 2-hydroxyl acylation and primer extension (SHAPE) assays revealed that CHIKV ؊1 PRF is stimulated by a tightly structured, triple-stem hairpin element, consistent with previous observations in alphaviruses, and that the TCR signal is composed of a single large multibulged hairpin element. These findings illuminate the roles of RNA structure in translational recoding and provide critical information relevant for design of live-attenuated vaccines against CHIKV and related viruses.

show abstract

“…These homopolymers do not confer any information regarding the reading frame (Crick et al, 1957). They induce frameshift mutations, meaning that nucleotides are ‘missed’ during DNA and RNA polymerizations (Atkins et al, 2016). These triplets also cause ribosomal slippage during protein translation (Klobutcher and Farabaugh, 2002; Ketteler, 2012; Advani and Dinman, 2016).…”

Section: Introductionmentioning

confidence: 99%

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

Houmami

Seligmann

2017

Front. Genet.

View full text Add to dashboard Cite

We present an evolutionary hypothesis assuming that signals marking nucleotide synthesis (DNA replication and RNA transcription) evolved from multi- to unidimensional structures, and were carried over from transcription to translation. This evolutionary scenario presumes that signals combining secondary and primary nucleotide structures are evolutionary transitions. Mitochondrial replication initiation fits this scenario. Some observations reported in the literature corroborate that several signals for nucleotide synthesis function in translation, and vice versa. (a) Polymerase-induced frameshift mutations occur preferentially at translational termination signals (nucleotide deletion is interpreted as termination of nucleotide polymerization, paralleling the role of stop codons in translation). (b) Stem-loop hairpin presence/absence modulates codon-amino acid assignments, showing that translational signals sometimes combine primary and secondary nucleotide structures (here codon and stem-loop). (c) Homopolymer nucleotide triplets (AAA, CCC, GGG, TTT) cause transcriptional and ribosomal frameshifts. Here we find in recently described human mitochondrial RNAs that systematically lack mono-, dinucleotides after each trinucleotide (delRNAs) that delRNA triplets include 2x more homopolymers than mitogenome regions not covered by delRNA. Further analyses of delRNAs show that the natural circular code X (a little-known group of 20 translational signals enabling ribosomal frame retrieval consisting of 20 codons {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} universally overrepresented in coding versus other frames of gene sequences), regulates frameshift in transcription and translation. This dual transcription and translation role confirms for X the hypothesis that translational signals were carried over from transcriptional signals.

show abstract

Ribosomal frameshifting and transcriptional slippage: From genetic steganography and cryptography to adventitious use

Cited by 239 publications

References 817 publications

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

Programmed Ribosomal Frameshifting Generates a Copper Transporter and a Copper Chaperone from the Same Gene

Functional and structural characterization of the chikungunya virus translational recoding signals

Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals

Contact Info

Product

Resources

About