DUSP11 and triphosphate RNA balance during virus infection

Choi, Joon Hwan; Sullivan, Christopher S.

doi:10.1371/journal.ppat.1009145

Cited by 8 publications

(7 citation statements)

References 32 publications

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“…[76] As for the two 5' cap-associated proteins, interferon-stimulated IFIT2 inhibits eukaryotic initiation factor 3 (eIF3)-mediated translation of viral RNAs without cap 2'-O-ribose methylation, a pathway coronaviruses are sensitized to by inhibiting nsp16's 2'-O-ribose methyltransferase activity, [77,78] and DUSP11 with 5'-triphosphatase and diphosphatase activity can either directly sensitize viral RNA to exoribonucleases as with hepatitis C virus (HCV) [79] or control RIG-I responses by altering viral or host triphosphate RNA balances. [80,81] RNA helicases are relatedly enriched yet as with 3CLpro cleavages have varying proviral and antiviral effects. Novel PLpro cleavages include neuron navigator 2, which possesses both helicase and exoribonuclease activity and is expressed in sensory nervous tissue susceptible to coronavirus infection, and DEAD box protein DDX42, which was recently shown to have broad antiviral activity including SARS-CoV-2 inhibition.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

Prescott¹

2021

Preprint

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A novel coronavirus (SARS-CoV-2) has caused a pandemic that has killed millions of people, worldwide vaccination and herd immunity are still far away, and few therapeutics are approved by regulatory agencies for widespread use. The coronavirus 3-chymotrypsin-like protease (3CLpro) is a commonly investigated target in COVID-19, however less work has been directed toward the equally important papain-like protease (PLpro). PLpro is less characterized due to its fewer and more diverse cleavages in coronavirus proteomes and the assumption that it mainly modulates host pathways with its deubiquitinating activity. Here, I extend my previous work on 3CLpro human cleavage prediction and enrichment/depletion analysis to PLpro. Using three sets of neural networks trained on different taxonomic ranks of dataset with a maximum of 463 different putative PLpro cleavages, Matthews correlation coefficients of 0.900, 0.948, and 0.966 were achieved for Coronaviridae, Betacoronavirus, and Sarbecovirus, respectively. I predict that more than 1,000 human proteins may be cleaved by PLpro depending on diversity of the training dataset and that many of these proteins are distinct from those previously predicted to be cleaved by 3CLpro. PLpro cleavages are similarly nonrandomly distributed and result in many annotations shared with 3CLpro cleavages including ubiquitination, poly(A) tail and 5' cap RNA binding proteins, helicases, and endogenous viral proteins. Combining PLpro with 3CLpro cleavage predictions, additional novel enrichment analysis was performed on known substrates of cleaved E3 ubiquitin ligases with results indicating that many pathways including viral RNA sensing are affected indirectly by E3 ligase cleavage independent of traditional PLpro deubiquitinating activity. As with 3CLpro, PLpro whole proteome cleavage prediction revealed many novel potential therapeutic targets against coronaviruses, although experimental verification is similarly required.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

Prescott¹

2021

Preprint

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“…Avoiding p1dsRNAs is particularly critical given that microRNAs are frequently presented as uncapped, 5’-monophosphorylated dsRNA molecules ( Ghildiyal and Zamore, 2009 ; Park et al, 2011 ). Abundant cellular p1dsRNAs also include mRNA degradation and triphosphorylase intermediates ( Braun et al, 2012 ; Choi et al, 2020 ; Choi and Sullivan, 2021 ; Jonas and Izaurralde, 2013 ; Nagarajan et al, 2013 ; van Dijk et al, 2002 ). The extreme, opposite responses to p2dsRNAs and p1dsRNAs indicate that RIG-I can sense the presence of a viral RNA by detecting a single chemical group: the β phosphate of p2dsRNAs and p3dsRNAs ( Ren et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands

Wang

Pyle²

2022

Molecular Cell

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“…Under normal physiological conditions, the 5ʹ-PPP termini of vtRNAs can be converted to 5ʹ-monophosphates (5ʹ-P) by the cellular triphosphatase dual-specificity phosphatase 11 (DUSP11), reducing their ability to trigger an innate immune response via RIG-I. However, during physiological stress events such as viral infections, DUSP11 can downregulate RIG-I expression, leading to an increase in the concentration of RNA species with 5ʹ-PPP groups at their terminal ends, thereby allowing recognition by RNA sensors and induction of the IFN response [ 46 , 47 , 82 ].…”

Section: Vault Rnas and Innate Immunitymentioning

confidence: 99%

“…This group of RNA Pol III-transcribed ncRNAs includes transfer RNAs (tRNAs), 7SL RNAs, 7SK RNAs, 5S rRNA, U6 small nuclear RNAs (snRNAs), YRNAs, Alu RNAs, and vault (vt) RNAs [ 38 – 43 ]. Furthermore, these ncRNAs have been linked to pathological processes associated with systemic inflammation, which is often driven by the abnormal production of interferon type I (IFN-I) [ 44 – 47 ].…”

Section: Introductionmentioning

confidence: 99%

Crosstalk between vault RNAs and innate immunity

Avila-Bonilla,

Martínez-Montero

2024

Mol Biol Rep

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Purpose Vault (vt) RNAs are noncoding (nc) RNAs transcribed by RNA polymerase III (RNA Pol III) with 5ʹ-triphosphate (5ʹ-PPP) termini that play significant roles and are recognized by innate immune sensors, including retinoic acid-inducible protein 1 (RIG-I). In addition, vtRNAs adopt secondary structures that can be targets of interferon-inducible protein kinase R (PKR) and the oligoadenylate synthetase (OAS)/RNase L system, both of which are important for activating antiviral defenses. However, changes in the expression of vtRNAs have been associated with pathological processes that activate proinflammatory pathways, which influence cellular events such as differentiation, aging, autophagy, apoptosis, and drug resistance in cancer cells. Results In this review, we summarized the biology of vtRNAs and focused on their interactions with the innate immune system. These findings provide insights into the diverse roles of vtRNAs and their correlation with various cellular processes to improve our understanding of their biological functions.

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DUSP11 and triphosphate RNA balance during virus infection

Cited by 8 publications

References 32 publications

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

SARS-CoV-2 PLpro whole human proteome cleavage prediction and enrichment/depletion analysis

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands

Crosstalk between vault RNAs and innate immunity

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