“Transfer” of power: The intersection of DNA virus infection and tRNA biology

Dremel, Sarah E; Jimenez, Ariana R; Tucker, Jessica M.

doi:10.1016/j.semcdb.2023.01.011

Cited by 4 publications

(4 citation statements)

References 116 publications

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“…The life cycle of many viruses has been linked to host tRNA biology (reviewed in (Dremel et al , 2023; Nunes et al , 2020)). In one well-known example, retroviruses such as HIV use cellular tRNAs as primers for reverse transcription and other viral functions (reviewed in (Jin & Musier-Forsyth, 2019).…”

Section: Introductionmentioning

confidence: 99%

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

Zhang

Ciesla

Eldin

et al. 2023

Preprint

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Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a common post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1-deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings suggest that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis and biology of SARS-CoV-2 infection.

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Section: Introductionmentioning

confidence: 99%

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

Zhang

Ciesla

Eldin

et al. 2023

Preprint

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“…It is believed that AMGs are referable in host recognition of the viruses for their potential to provide a competitive edge in viral life cycles and natural selection [75,77], though there is currently neither a definitive threshold nor a comparative baseline for the similarity between the two to give a credible match with statistical significance. Similar to tRNA genes carried by viruses that can enhance viral translation [78], possessing AMGs could alter host metabolism to favour viruses. The most common AMG found in the annotated NYMAGs is DNMT1, found on five NYMAGs.…”

Section: Host Predictionmentioning

confidence: 99%

Forty-nine metagenomic-assembled genomes from an aquatic virome expand Caudoviricetes by 45 potential new families and the newly uncovered Gossevirus of Bamfordvirae

Ni,

Chu,

Yan

et al. 2024

Journal of General Virology

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Twenty complete genomes (29–63 kb) and 29 genomes with an estimated completeness of over 90 % (30–90 kb) were identified for novel dsDNA viruses in the Yangshan Harbor metavirome. These newly discovered viruses contribute to the expansion of viral taxonomy by introducing 46 potential new families. Except for one virus, all others belong to the class Caudoviricetes. The exception is a novel member of the recently characterized viral group known as Gossevirus. Fifteen viruses were predicted to be temperate. The predicted hosts for the viruses appear to be involved in various aspects of the nitrogen cycle, including nitrogen fixation, oxidation and denitrification. Two viruses were identified to have a host of Flavobacterium and Tepidimonas fonticaldi, respectively, by matching CRISPR spacers with viral protospacers. Our findings provide an overview for characterizing and identifying specific viruses from Yangshan Harbor. The Gossevirus-like virus uncovered emphasizes the need for further comprehensive isolation and investigation of polinton-like viruses.

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“…In one well-known example, retroviruses such as HIV use cellular tRNAs as primers for reverse transcription and other viral functions (reviewed in (Jin & Musier-Forsyth, 2019 ). DNA and RNA viruses can also impact tRNA synthesis, processing, and charging to modulate infection and pathogenesis (Dremel et al, 2022 ;Netzer et al, 2009 ;Tucker et al, 2020 ). In a recent study, Chikungunya RNA virus infection has been shown to increase the expression of a human tRNA modification enzyme and alter tRNA modification patterns to favor viral protein expression (Jungfleisch et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…The life cycle of many viruses has been linked to host tRNA biology (reviewed in Dremel et al, 2023 ; Nunes et al, 2020 ). In one well-known example, retroviruses such as HIV use cellular tRNAs as primers for reverse transcription and other viral functions (reviewed in Jin and Musier-Forsyth, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

Zhang,

Eldin,

Ciesla

et al. 2024

eLife

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Nonstructural protein 5 (Nsp5) is the main protease of SARS-CoV-2 that cleaves viral polyproteins into individual polypeptides necessary for viral replication. Here, we show that Nsp5 binds and cleaves human tRNA methyltransferase 1 (TRMT1), a host enzyme required for a prevalent post-transcriptional modification in tRNAs. Human cells infected with SARS-CoV-2 exhibit a decrease in TRMT1 protein levels and TRMT1-catalyzed tRNA modifications, consistent with TRMT1 cleavage and inactivation by Nsp5. Nsp5 cleaves TRMT1 at a specific position that matches the consensus sequence of SARS-CoV-2 polyprotein cleavage sites, and a single mutation within the sequence inhibits Nsp5-dependent proteolysis of TRMT1. The TRMT1 cleavage fragments exhibit altered RNA binding activity and are unable to rescue tRNA modification in TRMT1-deficient human cells. Compared to wildtype human cells, TRMT1-deficient human cells infected with SARS-CoV-2 exhibit reduced levels of intracellular viral RNA. These findings provide evidence that Nsp5-dependent cleavage of TRMT1 and perturbation of tRNA modification patterns contribute to the cellular pathogenesis of SARS-CoV-2 infection.

show abstract

“Transfer” of power: The intersection of DNA virus infection and tRNA biology

Cited by 4 publications

References 116 publications

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

Forty-nine metagenomic-assembled genomes from an aquatic virome expand Caudoviricetes by 45 potential new families and the newly uncovered Gossevirus of Bamfordvirae

Proteolytic cleavage and inactivation of the TRMT1 tRNA modification enzyme by SARS-CoV-2 main protease

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