Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication

Gerresheim, Gesche K.; Hess, Carolin S; Shalamova, Lyudmila; Fricke, Markus; Marz, Manja; Andreev, Dmitry E.; Shatsky, Ivan N.; Niepmann, Michael

doi:10.3390/ijms21186955

Cited by 4 publications

(4 citation statements)

References 103 publications

(212 reference statements)

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“…by flexible structural intermediates. Selection pressures that act independently, i.e., in different functional contexts, to preserve sequence and secondary structure are particularly conducive to incongruent patterns 42 , 72 , 73 such as the ones in the 5BSL2 stem-loop structure.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus

Triebel,

Lamkiewicz,

Ontiveros

et al. 2024

Sci Rep

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Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large ‘cloud’ of RNA genomes (quasispecies) which—by trial and error—comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.

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Section: Resultsmentioning

confidence: 99%

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus

Triebel,

Lamkiewicz,

Ontiveros

et al. 2024

Sci Rep

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show abstract

“…by flexible structural intermediates. Selection pressures act independently, i.e., in different functional contexts, to preserve sequence and secondary structure are particularly conducive to incongruent patterns [36, 60, 61] such as the ones in the 5BSL2 stem-loop structure.…”

Section: Resultsmentioning

confidence: 99%

“…*** -During the review process of this manuscript, Rfam numbers will substituted here. conducive to incongruent patterns [36,60,61] such as the ones in the 5BSL2 stem-loop structure.…”

Section: ---------( ( ( ( ( ( ( [ ( ( ( ( ( -----) ) ) ) ) ] ) ) ) ) ...mentioning

confidence: 99%

Comprehensive Survey of Conserved RNA Secondary Structures in Full-Genome Alignment of Hepatitis C Virus

Triebel,

Lamkiewicz,

Ontiveros

et al. 2023

Preprint

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Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large “cloud” of RNA genomes which - by trial and error - comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements.Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies.Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches ofHepacivirus Care provided in the supplement.

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“…Interestingly, some enrichments of rare codon occur in the 5′‐ or 3′‐termini of CDSs. This 5′‐ and 3′‐terminal enrichment has been linked to membrane targeting or protein secretion and to translation termination, respectively (Clarke & Clark, 2010 ; Gerresheim et al., 2020 ). In the chloroplast, significant enrichment of the 5′‐terminus with rare codons occurs for example in psaA , psaB , psbB , rps3 , or ycf1 , and this occurs at the 3′‐terminus in rps4 or rps7 .…”

Section: Resultsmentioning

confidence: 99%

Mechanisms governing codon usage bias and the implications for protein expression in the chloroplast of Chlamydomonas reinhardtii

2022

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Chloroplasts possess a considerably reduced genome that is decoded via an almost minimal set of tRNAs. These features make an excellent platform for gaining insights into fundamental mechanisms that govern protein expression. Here, we present a comprehensive and revised perspective of the mechanisms that drive codon selection in the chloroplast of Chlamydomonas reinhardtii and the functional consequences for protein expression. In order to extract this information, we applied several codon usage descriptors to genes with different expression levels. We show that highly expressed genes strongly favor translationally optimal codons, while genes with lower functional importance are rather affected by directional mutational bias. We demonstrate that codon optimality can be deduced from codon-anticodon pairing affinity and, for a small number of amino acids (leucine, arginine, serine, and isoleucine), tRNA concentrations. Finally, we review, analyze, and expand on the impact of codon usage on protein yield, secondary structures of mRNA, translation initiation and termination, and amino acid composition of proteins, as well as cotranslational protein folding. The comprehensive analysis of codon choice provides crucial insights into heterologous gene expression in the chloroplast of C. reinhardtii, which may also be applicable to other chloroplastcontaining organisms and bacteria.

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Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication

Cited by 4 publications

References 103 publications

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus

Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus

Comprehensive Survey of Conserved RNA Secondary Structures in Full-Genome Alignment of Hepatitis C Virus

Mechanisms governing codon usage bias and the implications for protein expression in the chloroplast of Chlamydomonas reinhardtii

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