eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation.
Biochim Biophys Acta Gene Regul Mech
; 1860(7): 761-772, 2017 Jul.
Article
em En
| MEDLINE
| ID: mdl-28487214
ABSTRACT
Post-transcriptional gene regulation is an important step in eukaryotic gene expression. The last step to govern production of nascent peptides is during the process of mRNA translation. mRNA translation is controlled by many translation initiation factors that are susceptible to post-translational modifications. Here we report that one of the translation initiation factors, eIF4E, is phosphorylated by Mammalian Ste20-like kinase (MST1). Upon phosphorylation, eIF4E weakly interacts with the 5' CAP to inhibit mRNA translation. Simultaneously, active polyribosome is more associated with long noncoding RNAs (lncRNAs). Moreover, the linc00689-derived micropeptide, STORM (Stress- and TNF-α-activated ORF Micropeptide), is triggered by TNF-α-induced and MST1-mediated eIF4E phosphorylation, which exhibits molecular mimicry of SRP19 and, thus, competes for 7SL RNA. Our findings have uncovered a novel function of MST1 in mRNA and lncRNA translation by direct phosphorylation of eIF4E. This novel signaling pathway will provide new platforms for regulation of mRNA translation via post-translational protein modification.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosforilação
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Biossíntese de Proteínas
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RNA Mensageiro
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Proteínas Proto-Oncogênicas
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Fator de Crescimento de Hepatócito
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Fator de Iniciação 4E em Eucariotos
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RNA Longo não Codificante
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta Gene Regul Mech
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos