Most synonymous allelic variants in HIV tat are not silent.
Codon usage
HIV
RNA stability
Silent
Synonymous
Tat
Variant
Journal
Genomics
ISSN: 1089-8646
Titre abrégé: Genomics
Pays: United States
ID NLM: 8800135
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
19
11
2022
revised:
12
02
2023
accepted:
03
03
2023
medline:
25
5
2023
pubmed:
10
3
2023
entrez:
9
3
2023
Statut:
ppublish
Résumé
The genetic code has degenerate codons that produce no change in the translated protein sequence and are generally thought to be silent. However, some synonymous variants are clearly not silent. Herein, we questioned the frequency of non-silent synonymous variants. We tested how random synonymous variants in the HIV Tat transcription factor effect transcription of an LTR-GFP reporter. Our model system has the advantage of directly measuring the function of the gene in human cells. Approximately, 67% of synonymous variants in Tat were non-silent, either having reduced activity or were full loss-of-function alleles. Eight mutant codons had higher codon usage than wild type, accompanied by reduced transcriptional activity. These were clustered on a loop in the Tat structure. We conclude that most synonymous Tat variants are not silent in human cells, and 25% are associated with changes in codon usage, likely effecting protein folding.
Identifiants
pubmed: 36893872
pii: S0888-7543(23)00047-2
doi: 10.1016/j.ygeno.2023.110603
pmc: PMC10257815
mid: NIHMS1903390
pii:
doi:
Substances chimiques
Codon
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110603Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM121325
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI116411
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest CJG, JIR, and MRS authors work for Heligenics that uses the GigaAssay technology for commercial drug development, drug discovery and diagnostics. There is a potential conflict of interest as the impact of the non-silent variant rate could benefit Heligenics pursuit to produce data that improves genetic testing.
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