A frameshift in time

Yordanova, Martina M.; Baranov, Pavel V.

doi:10.7554/elife.78373

eLife

2022

DOI: 10.7554/elife.78373

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A frameshift in time

Martina M. Yordanova

Pavel V. Baranov

Abstract: The efficiency with which ribosomes shift reading frames when decoding viral RNA may change over the course of an infection.

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Cited by 4 publications

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“…In CoVs the slippage occurs by 1 nucleotide in the backward direction. The frameshifting process achieves the optimal proportions of viral protein products, where proteins needed in large quantities are usually encoded early in the sequence in an open reading frame ORF1A, and those required in lower quantities are encoded in a later overlapping downstream reading frame (ORF1B) ( 1 ). The upstream ORF of CoVs encodes nonstructural proteins.…”

mentioning

confidence: 99%

Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability

Yan,

Zhu,

Hohl

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The frameshifting RNA element (FSE) in coronaviruses (CoVs) regulates the programmed −1 ribosomal frameshift (−1 PRF) mechanism common to many viruses. The FSE is of particular interest as a promising drug candidate. Its associated pseudoknot or stem loop structure is thought to play a large role in frameshifting and thus viral protein production. To investigate the FSE structural evolution, we use our graph theory-based methods for representing RNA secondary structures in the RNA-As-Graphs (RAG) framework to calculate conformational landscapes of viral FSEs with increasing sequence lengths for representative 10 Alpha and 13 Beta-CoVs. By following length-dependent conformational changes, we show that FSE sequences encode many possible competing stems which in turn favor certain FSE topologies, including a variety of pseudoknots, stem loops, and junctions. We explain alternative competing stems and topological FSE changes by recurring patterns of mutations. At the same time, FSE topology robustness can be understood by shifted stems within different sequence contexts and base pair coevolution. We further propose that the topology changes reflected by length-dependent conformations contribute to tuning the frameshifting efficiency. Our work provides tools to analyze virus sequence/structure correlations, explains how sequence and FSE structure have evolved for CoVs, and provides insights into potential mutations for therapeutic applications against a broad spectrum of CoV FSEs by targeting key sequence/structural transitions.

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mentioning

confidence: 99%

Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability

Yan,

Zhu,

Hohl

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Re-reading the genetic code: The evolutionary potential of frameshifting in time

Samhita

2022

J Biosci

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Nontriplet feature of genetic code in Euplotes ciliates is a result of neutral evolution

Gaydukova

Moldovan

Vallesi

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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The triplet nature of the genetic code is considered a universal feature of known organisms. However, frequent stop codons at internal mRNA positions in Euplotes ciliates ultimately specify ribosomal frameshifting by one or two nucleotides depending on the context, thus posing a nontriplet feature of the genetic code of these organisms. Here, we sequenced transcriptomes of eight Euplotes species and assessed evolutionary patterns arising at frameshift sites. We show that frameshift sites are currently accumulating more rapidly by genetic drift than they are removed by weak selection. The time needed to reach the mutational equilibrium is several times longer than the age of Euplotes and is expected to occur after a several-fold increase in the frequency of frameshift sites. This suggests that Euplotes are at an early stage of the spread of frameshifting in expression of their genome. In addition, we find the net fitness burden of frameshift sites to be noncritical for the survival of Euplotes . Our results suggest that fundamental genome-wide changes such as a violation of the triplet character of genetic code can be introduced and maintained solely by neutral evolution.

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A frameshift in time

Abstract: The efficiency with which ribosomes shift reading frames when decoding viral RNA may change over the course of an infection.

Cited by 4 publications

References 9 publications

Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability

Evolution of coronavirus frameshifting elements: Competing stem networks explain conservation and variability

Re-reading the genetic code: The evolutionary potential of frameshifting in time

Nontriplet feature of genetic code in Euplotes ciliates is a result of neutral evolution

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