Effects of messenger RNA structure and other translational control mechanisms on major histocompatibility complex‐I mediated antigen presentation

Murat, Pierre; Tellam, Judy

doi:10.1002/wrna.1262

Cited by 7 publications

(6 citation statements)

References 77 publications

(194 reference statements)

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“…Hence, PhenDC3 and more generally G4 ligands represent chemical probes that will greatly help to characterize this pathway and to identify its physiological mRNA targets. To finish, as other oncogenic gamma herpesviruses like the Kaposi sarcoma-associated herpesvirus have evolved similar strategy of G4 clustering in the central coding regions of their GMP to evade the immune system, the results presented here may have applications for other gammaherpesviruses-related diseases2937.…”

Section: Discussionmentioning

confidence: 83%

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

et al. 2017

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The oncogenic Epstein-Barr virus (EBV) evades the immune system but has an Achilles heel: its genome maintenance protein EBNA1, which is essential for viral genome maintenance but highly antigenic. EBV has seemingly evolved a system in which the mRNA sequence encoding the glycine-alanine repeats (GAr) of the EBNA1 protein limits its expression to the minimal level necessary for function while minimizing immune recognition. Here, we identify nucleolin (NCL) as a host factor required for this process via a direct interaction with G-quadruplexes formed in GAr-encoding mRNA sequence. Overexpression of NCL enhances GAr-based inhibition of EBNA1 protein expression, whereas its downregulation relieves the suppression of both expression and antigen presentation. Moreover, the G-quadruplex ligand PhenDC3 prevents NCL binding to EBNA1 mRNA and reverses GAr-mediated repression of EBNA1 expression and antigen presentation. Hence the NCL-EBNA1 mRNA interaction is a relevant therapeutic target to trigger an immune response against EBV-carrying cancers.

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Section: Discussionmentioning

confidence: 83%

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

et al. 2017

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“…doi:10.1093/molbev/msab049 MBE 2005). We also note that viral RNA secondary structures have been implicated in the suppression of antigen presentation (EBNA-1; Apcher et al 2010;Tellam et al 2012) and in the suppression of host innate immune responses (Vandevenne et al 2010;McFadden et al 2013;Witteveldt et al 2014;Murat and Tellam 2015). We believe that detailed experimental evaluation of both s2m function and the possible phenotypic consequences of changes observed among SARS-CoV-2 isolates should represent a priority topic in coronavirus research.…”

Section: Discussionmentioning

confidence: 90%

Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2

Chiara

Horner

Gissi

et al. 2021

Molecular Biology and Evolution

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Effective systems for the analysis of molecular data are fundamental for monitoring the spread of infectious diseases and studying pathogen evolution. The rapid identification of emerging viral strains, and/or genetic variants potentially associated with novel phenotypic features is one of the most important objectives of genomic surveillance of human pathogens and represents one of the first lines of defense for the control of their spread. During the COVID 19 pandemic, several taxonomic frameworks have been proposed for the classification of SARS-Cov-2 isolates. These systems, which are typically based on phylogenetic approaches, represent essential tools for epidemiological studies as well as contributing to the study of the origin of the outbreak. Here we propose an alternative, reproducible and transparent phenetic method to study changes in SARS-CoV-2 genomic diversity over time. We suggest that our approach can complement other systems and facilitate the identification of biologically relevant variants in the viral genome. To demonstrate the validity of our approach, we present comparative genomic analyses of more than 175,000 genomes. Our method delineates 22 distinct SARS-CoV-2 haplogroups, which, based on the distribution of high frequency genetic variants, fall into 4 major macro haplogroups. We highlight biased spatio-temporal distributions of SARS-CoV-2 genetic profiles and show that 7 of the 22 haplogroups (and of all of the 4 haplogroup clusters) showed a broad geographic distribution within China by the time the outbreak was widely recognised—suggesting early emergence and widespread cryptic circulation of the virus well before its isolation in January 2020. General patterns of genomic variability are remarkably similar within all major SARS-CoV-2 haplogroups, with UTRs consistently exhibiting the greatest variability, with s2m, a conserved secondary structure element of unknown function in the 3’ UTR of the viral genome showing evidence of a functional shift. While several polymorphic sites that are specific to one or more haplogroups were predicted to be under positive or negative selection, overall our analyses suggest that the emergence of novel types is unlikely to be driven by convergent evolution and independent fixation of advantageous substitutions, or by selection of recombined strains. In the absence of extensive clinical metadata for most available genome sequences, and in the context of extensive geographic and temporal biases in the sampling, many questions regarding the evolution and clinical characteristics of SARS-CoV-2 isolates remain open. However, our data indicate that the approach outlined here can be usefully employed in the identification of candidate SARS-CoV-2 genetic variants of clinical and epidemiological importance.

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“…Notably, we observed that some features enriched in MAP source genes are also common in viral genes (e.g., internal disorder and 5′ UTR secondary structures). Indeed, disorder is prevalent in viral genomes (65), and several viral transcripts contain complex 5′ UTR secondary structures that stall ribosomal translation (66).…”

Section: Discussionmentioning

confidence: 99%

MHC class I–associated peptides derive from selective regions of the human genome

Pearson¹,

Daouda²,

Granados³

et al. 2016

Journal of Clinical Investigation

181

218

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Effects of messenger RNA structure and other translational control mechanisms on major histocompatibility complex‐I mediated antigen presentation

Cited by 7 publications

References 77 publications

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

Nucleolin directly mediates Epstein-Barr virus immune evasion through binding to G-quadruplexes of EBNA1 mRNA

Comparative Genomics Reveals Early Emergence and Biased Spatiotemporal Distribution of SARS-CoV-2

MHC class I–associated peptides derive from selective regions of the human genome

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