Extracurricular Functions of tRNA Modifications in Microorganisms

Edwards, A.; Addo, Maame A; Santos, Patricia C. Dos

doi:10.3390/genes11080907

Cited by 23 publications

(16 citation statements)

References 129 publications

(169 reference statements)

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“…acp3U) events. Though these modifications have not yet been reported to occur on mRNA, both can occur on tRNA [62,63]. Finally, A-to-G events are also evident and the likely result of adenosine deamination to inosine, decoded as guanosine, which is catalyzed by ADAR proteins, whose preference for dsRNA targets could attract them to double-stranded RNA intermediates of the viral replication process (the prominent G clade mutation (D614G) may be the outcome of an A-to-I deamination event at position A23403).…”

Section: Mutational Pattern In Sars-cov-2 May Reveal Intrinsic Cause Of Genetic Diversitymentioning

confidence: 95%

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

Tasakis

Samaras

Jamison³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year and a half has caused 3.56 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, end of the year data and 2021 revealed the gradual increase to prevalence of known variants of concern, particularly B.1.1.7, that have acquired additional Spike mutations. Overall, our results suggest that predominant viral genomes are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may become problematic when super-spreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.

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Section: Mutational Pattern In Sars-cov-2 May Reveal Intrinsic Cause Of Genetic Diversitymentioning

confidence: 95%

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

Tasakis

Samaras

Jamison³

et al. 2021

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…RNA-membrane localization in a gel membrane system could be controlled by shifting the temperature above and below the membrane gel-liquid transition temperature, thereby turning on and off RNA-membrane binding. Membrane localization could also be regulated dynamically through enzymatic modification [56][57][58] of RNA. Lipid-dependent sorting and aggregation of RNAs could have played a role in primordial scenarios, where one of the biggest challenges was to increase concentration of molecules.…”

Section: Discussionmentioning

confidence: 99%

Lipid membranes modulate the activity of RNA through sequence-dependent interactions

Czerniak

Sáenz

2021

Preprint

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RNA is a ubiquitous biomolecule that can serve as both catalyst and information carrier. Understanding how RNA activity is controlled and how it in turn regulates bioactivity is crucial for elucidating its physiological roles and potential applications in synthetic biology. Here we show that lipid membranes can act as RNA organization platforms, introducing a novel mechanism for ribo-regulation. The activity of R3C ribozyme can be modified by the presence of lipid membranes, with RNA-lipid interactions dependent on RNA sequence, structure and length. In particular, the presence of guanine in short RNAs is crucial for RNA-lipid interactions, while double-stranded RNAs further increase lipid-binding affinity. Lastly, by artifially modifying the R3C-substrate sequence to enhance membrane binding we unexpectedly generated a lipid sensitive riboswitch. These findings introduce RNA-lipid interactions as a tool for developing riboswitches and novel RNA-based lipid biosensors, and bear significant implications for RNA World scenarios for the origin of life.

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“…acp3U) events. Though these modifications have not yet been reported to occur on mRNA, both can occur on tRNA [54, 55]. Finally, A-to-G events are also evident (and the likely result of adenosine deamination to inosine, decoded as guanosine, which is catalyzed by ADAR proteins, whose preference for dsRNA targets could attract them to double-stranded RNA intermediates of the viral replication process) – for example the prominent G clade mutation (D614G) may be the outcome of an A-to-I deamination event at position A23403).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

Tasakis

Samaras

Jamison³

et al. 2021

Preprint

View full text Add to dashboard Cite

Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year has caused 2.29 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development. Our study explores evolution of SARS-CoV-2 in a representative cohort of sequences covering the entire genome in the United States, through all of 2020 and early 2021. Strikingly, we detected many accumulating Single Nucleotide Variations (SNVs) encoding amino acid changes in the SARS-CoV-2 genome, with a pattern indicative of RNA editing enzymes as major mutators of SARS-CoV-2 genomes. We report three major variants through October of 2020. These revealed 14 key mutations that were found in various combinations among 14 distinct predominant signatures. These signatures likely represent evolutionary lineages of SARS-CoV-2 in the U.S. and reveal clues to its evolution such as a mutational burst in the summer of 2020 likely leading to a homegrown new variant, and a trend towards higher mutational load among viral isolates, but with occasional mutation loss. The last quartile of 2020 revealed a concerning accumulation of mostly novel low frequency replacement mutations in the Spike protein, and a hypermutable glutamine residue near the putative furin cleavage site. Finally, the end of the year data revealed the presence of known variants of concern including B.1.1.7, which has acquired additional Spike mutations. Overall, our results suggest that predominant viral sequences are dynamically evolving over time, with periods of mutational bursts and unabated mutation accumulation. This high level of existing variation, even at low frequencies and especially in the Spike-encoding region may be become problematic when superspreader events, akin to serial Founder Events in evolution, drive these rare mutations to prominence.

show abstract

Extracurricular Functions of tRNA Modifications in Microorganisms

Cited by 23 publications

References 129 publications

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

Lipid membranes modulate the activity of RNA through sequence-dependent interactions

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts

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