Differential Effects on the Translation of Immune-Related Alternatively Polyadenylated mRNAs in Melanoma and T Cells by eIF4A Inhibition.
STAT1
alternative polyadenylation
eIF4A
immune checkpoints
intronic polyadenylation
melanoma
silvestrol
translation
Journal
Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829
Informations de publication
Date de publication:
24 Feb 2022
24 Feb 2022
Historique:
received:
20
01
2022
revised:
20
02
2022
accepted:
21
02
2022
entrez:
10
3
2022
pubmed:
11
3
2022
medline:
11
3
2022
Statut:
epublish
Résumé
Targeting the translation initiation complex eIF4F, which binds the 5' cap of mRNAs, is a promising anti-cancer approach. Silvestrol, a small molecule inhibitor of eIF4A, the RNA helicase component of eIF4F, inhibits the translation of the mRNA encoding the signal transducer and activator of transcription 1 (STAT1) transcription factor, which, in turn, reduces the transcription of the gene encoding one of the major immune checkpoint proteins, i.e., programmed death ligand-1 (PD-L1) in melanoma cells. A large proportion of human genes produce multiple mRNAs differing in their 3'-ends through the use of alternative polyadenylation (APA) sites, which, when located in alternative last exons, can generate protein isoforms, as in the
Identifiants
pubmed: 35267483
pii: cancers14051177
doi: 10.3390/cancers14051177
pmc: PMC8909304
pii:
doi:
Types de publication
Journal Article
Langues
eng
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