Acetylation of Cytidine Residues Boosts HIV-1 Gene Expression by Increasing Viral RNA Stability. Cell Host Microbe 2020 Aug 12;28(2):306-312.e6
Date
06/14/2020Pubmed ID
32533923Pubmed Central ID
PMC7429276DOI
10.1016/j.chom.2020.05.011Scopus ID
2-s2.0-85086394689 (requires institutional sign-in at Scopus site) 159 CitationsAbstract
Epitranscriptomic RNA modifications, including methylation of adenine and cytidine residues, are now recognized as key regulators of both cellular and viral mRNA function. Moreover, acetylation of the N4 position of cytidine (ac4C) was recently reported to increase the translation and stability of cellular mRNAs. Here, we show that ac4C and N-acetyltransferase 10 (NAT10), the enzyme that adds ac4C to RNAs, have been subverted by human immunodeficiency virus 1 (HIV-1) to increase viral gene expression. HIV-1 transcripts are modified with ac4C at multiple discrete sites, and silent mutagenesis of these ac4C sites led to decreased HIV-1 gene expression. Similarly, loss of ac4C from viral transcripts due to depletion of NAT10 inhibited HIV-1 replication by reducing viral RNA stability. Interestingly, the NAT10 inhibitor remodelin could inhibit HIV-1 replication at concentrations that have no effect on cell viability, thus identifying ac4C addition as a potential target for antiviral drug development.
Author List
Tsai K, Jaguva Vasudevan AA, Martinez Campos C, Emery A, Swanstrom R, Cullen BRAuthor
Anand Jaguva Vasudevan PhD, BS, MSc Research Scientist I in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AcetylationCell Line
Cytidine
Female
Gene Expression
Gene Expression Regulation, Viral
HEK293 Cells
HIV-1
Humans
Hydrazones
Male
N-Terminal Acetyltransferases
RNA Stability
RNA, Viral
Thiazoles
Virus Replication
