Assessing eukaryotic initiation factor 4F subunit essentiality by CRISPR-induced gene ablation in the mouse.
GEMM
Translation
eIF4A1
eIF4A2
eIF4E
eIF4G1
eIF4G3
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
18
06
2021
accepted:
10
09
2021
revised:
31
08
2021
pubmed:
25
9
2021
medline:
9
11
2021
entrez:
24
9
2021
Statut:
ppublish
Résumé
Eukaryotic initiation factor (eIF) 4F plays a central role in the ribosome recruitment phase of cap-dependent translation. This heterotrimeric complex consists of a cap binding subunit (eIF4E), a DEAD-box RNA helicase (eIF4A), and a large bridging protein (eIF4G). In mammalian cells, there are two genes encoding eIF4A (eIF4A1 and eIF4A2) and eIF4G (eIF4G1 and eIF4G3) paralogs that can assemble into eIF4F complexes. To query the essential nature of the eIF4F subunits in normal development, we used CRISPR/Cas9 to generate mouse strains with targeted ablation of each gene encoding the different eIF4F subunits. We find that Eif4e, Eif4g1, and Eif4a1 are essential for viability in the mouse, whereas Eif4g3 and Eif4a2 are not. However, Eif4g3 and Eif4a2 do play essential roles in spermatogenesis. Crossing of these strains to the lymphoma-prone Eμ-Myc mouse model revealed that heterozygosity at the Eif4e or Eif4a1 loci significantly delayed tumor onset. Lastly, tumors derived from Eif4e
Identifiants
pubmed: 34559254
doi: 10.1007/s00018-021-03940-5
pii: 10.1007/s00018-021-03940-5
doi:
Substances chimiques
Eukaryotic Initiation Factor-4F
0
Protein Subunits
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6709-6719Subventions
Organisme : CIHR
ID : FDN-148366
Pays : Canada
Organisme : CIHR
ID : FDN-148366
Pays : Canada
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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