Translation termination codons in protein synthesis and disease

Lombardi, Silvia; Testa, Maria Francesca; Pinotti, Mirko; Branchini, Alessio

doi:10.1016/bs.apcsb.2022.06.001

Cited by 4 publications

(2 citation statements)

References 220 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, we recently understood that such stop codons are used for the regulation of protein expression at the ribosome level in procaryotes 87,88 and that some mechanisms can promote ribosome readthrough in vertebrates [89][90][91][92] . Moreover, molecules were proposed for therapeutic strategies promoting such ribosome readthrough in human genetic diseases with stop codons impairing the production of physiological proteins [93][94][95] . Therefore, such ribosome readthrough might be possible for HERV genes in human cells.…”

Section: Resultsmentioning

confidence: 99%

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

Brunel,

Paganini,

Galloux

et al. 2024

Preprint

View full text Add to dashboard Cite

The human genome comprises 8% of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-WENV-U3RRNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-WENVRNA origin in these patients, but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.

show abstract

Section: Resultsmentioning

confidence: 99%

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

Brunel,

Paganini,

Galloux

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The mutation-agnostic PTC readthrough therapy is an appealing treatment strategy to target multiple indications caused by a common PTC (UAA, UAG, or UGA) [ 31 ]. Use of small molecules as therapeutic readthrough agents was reviewed recently [ [32] , [33] , [34] , [35] , [36] ].…”

Section: Introductionmentioning

confidence: 99%