Schlafen14 Impairs HIV-1 Expression in a Codon Usage-Dependent Manner

Schlafen (SLFN) is a family of proteins upregulated by type I interferons with a regulatory role in translation. Intriguingly, SLFN14 associates with the ribosome and can degrade rRNA, tRNA, and mRNA in vitro, but a role in translation is still unknown. Ribosomes are important regulatory hubs during...

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Bibliographic Details
Published in:Viruses 2024-04, Vol.16 (4), p.502
Main Authors: Valenzuela, Carlos, Saucedo, Sergio, Llano, Manuel
Format: Article
Language:English
Subjects:
Antibodies
Bias
Calcium phosphates
Chicken pox
Cloning
Codon
Codon - genetics
Codon Usage
codon usage bias
Codons
Control
Gag protein
Gene Expression Regulation, Viral
Glycoproteins
Health aspects
HEK293 Cells
HIV
HIV (Viruses)
HIV Infections - genetics
HIV Infections - virology
HIV-1
HIV-1 - genetics
HIV-1 - physiology
Human immunodeficiency virus
Humans
Infections
Influenza
Mutagenesis
Penicillin
Plasmids
Protein Biosynthesis
Protein expression
Proteins
Ribonucleic acid
ribosome
Ribosomes
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
rRNA
Schlafen14
Transfer RNA
translation
Translation elongation
tRNA
Viral infections
Virus Replication
Viruses
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Description
Summary:Schlafen (SLFN) is a family of proteins upregulated by type I interferons with a regulatory role in translation. Intriguingly, SLFN14 associates with the ribosome and can degrade rRNA, tRNA, and mRNA in vitro, but a role in translation is still unknown. Ribosomes are important regulatory hubs during translation elongation of mRNAs rich in rare codons. Therefore, we evaluated the potential role of SLFN14 in the expression of mRNAs enriched in rare codons, using HIV-1 genes as a model. We found that, in a variety of cell types, including primary immune cells, SLFN14 regulates the expression of HIV-1 and non-viral genes based on their codon adaptation index, a measurement of the synonymous codon usage bias; consequently, SLFN14 inhibits the replication of HIV-1. The potent inhibitory effect of SLFN14 on the expression of the rare codon-rich transcript HIV-1 Gag was minimized by codon optimization. Mechanistically, we found that the endoribonuclease activity of SLFN14 is required, and that ribosomal RNA degradation is involved. Therefore, we propose that SLFN14 impairs the expression of HIV-1 transcripts rich in rare codons, in a catalytic-dependent manner.
ISSN:1999-4915
1999-4915
DOI:10.3390/v16040502