eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation

Kyung Won Min, Sylvia Davila, Richard W. Zealy, Lawson T. Lloyd, In Young Lee, Rumi Lee, Kyung Hye Roh, Ahjin Jung, Jacek Jemielity, Eui Ju Choi, Jeong Ho Chang, Je Hyun Yoon

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)761-772
Number of pages12
JournalBiochimica et Biophysica Acta - Gene Regulatory Mechanisms
Volume1860
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

Keywords

  • eIF4E phosphorylation
  • Long noncoding RNA
  • MST1
  • Post-transcriptional modification
  • Translation

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Min, K. W., Davila, S., Zealy, R. W., Lloyd, L. T., Lee, I. Y., Lee, R., Roh, K. H., Jung, A., Jemielity, J., Choi, E. J., Chang, J. H., & Yoon, J. H. (2017). eIF4E phosphorylation by MST1 reduces translation of a subset of mRNAs, but increases lncRNA translation. Biochimica et Biophysica Acta - Gene Regulatory Mechanisms, 1860(7), 761-772. https://doi.org/10.1016/j.bbagrm.2017.05.002