Eukaryotic Initiation Factor 5A2 Regulates Expression of Antiviral Genes.
J Mol Biol
; 434(10): 167564, 2022 05 30.
Article
in En
| MEDLINE
| ID: mdl-35358571
ABSTRACT
Translation factors are essential for regulation of protein synthesis. The eukaryotic translation initiation factor 5A (eIF5A) family is made up of two paralogues - eIF5A1 and eIF5A2 - which display high sequence homology but distinct tissue tropism. While eIF5A1 directly binds to the ribosome and regulates translation initiation, elongation, and termination, the molecular function of eIF5A2 remains poorly understood. Here, we engineer an eIF5A2 knockout allele in the SW480 colon cancer cell line. Using ribosome profiling and RNA-Sequencing, we reveal that eIF5A2 is functionally distinct from eIF5A1 and does not regulate transcript-specific or global protein synthesis. Instead, eIF5A2 knockout leads to decreased intrinsic antiviral gene expression, including members of the IFITM and APOBEC3 family. Furthermore, cells lacking eIF5A2 display increased permissiveness to virus infection. Our results uncover eIF5A2 as a factor involved regulating the antiviral transcriptome, and reveal an example of how gene duplications of translation factors can result in proteins with distinct functions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Diseases
/
Peptide Initiation Factors
/
Gene Expression Regulation
/
RNA-Binding Proteins
/
Eukaryotic Initiation Factor-5
Limits:
Humans
Language:
En
Journal:
J Mol Biol
Year:
2022
Document type:
Article
Affiliation country:
Estados Unidos