eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle

Incheol Ryu, You Sub Won, Hongseok Ha, Eunjin Kim, Yeonkyoung Park, Min Kyung Kim, Do Hoon Kwon, Junho Choe, Hyun Kyu Song, Hosung Jung, Yoon Ki Kim

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Exon junction complexes (EJCs) loaded onto spliced mRNAs during splicing serve as molecular markers for various post-transcriptional gene-regulatory processes, including nonsense-mediated mRNA decay (NMD). Although the composition and structure of EJCs are well characterized, the mechanism regulating EJC deposition remains unknown. Here we find that threonine 163 (T163) within the RNA-binding motif of eIF4A3 (a core EJC component) is phosphorylated by cyclin-dependent protein kinases 1 and 2 in a cell cycle-dependent manner. T163 phosphorylation hinders binding of eIF4A3 to spliced mRNAs and other EJC components. Instead, it promotes association of eIF4A3 with CWC22, which guides eIF4A3 to an active spliceosome. These molecular events ensure the fidelity of specific deposition of the EJC ∼20–24 nt upstream of an exon-exon junction. Accordingly, NMD is affected by T163 phosphorylation. Collectively, our data provide evidence that T163 phosphorylation affects EJC formation and, consequently, NMD efficiency in a cell cycle-dependent manner. Ryu et al. show that eIF4A3 (a core EJC component) is phosphorylated at the threonine 163 position by CDK1 and CDK2 in a cell cycle-dependent manner. This event triggers EJC remodeling and affects NMD efficiency in a cell cycle-dependent manner.

Original languageEnglish
Pages (from-to)2126-2139.e9
JournalCell Reports
Volume26
Issue number8
DOIs
Publication statusPublished - 2019 Feb 19

Fingerprint

Nonsense Mediated mRNA Decay
Phosphorylation
Exons
Cell Cycle
Cells
Messenger RNA
Threonine
CDC2 Protein Kinase
Cyclin-Dependent Kinase 2
Spliceosomes
Cyclin-Dependent Kinases
Regulator Genes

Keywords

  • CDK
  • cell cycle
  • eIF4A3
  • exon junction complex
  • nonsense-mediated mRNA decay
  • phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ryu, I., Won, Y. S., Ha, H., Kim, E., Park, Y., Kim, M. K., ... Kim, Y. K. (2019). eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. Cell Reports, 26(8), 2126-2139.e9. https://doi.org/10.1016/j.celrep.2019.01.101

eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. / Ryu, Incheol; Won, You Sub; Ha, Hongseok; Kim, Eunjin; Park, Yeonkyoung; Kim, Min Kyung; Kwon, Do Hoon; Choe, Junho; Song, Hyun Kyu; Jung, Hosung; Kim, Yoon Ki.

In: Cell Reports, Vol. 26, No. 8, 19.02.2019, p. 2126-2139.e9.

Research output: Contribution to journalArticle

Ryu, I, Won, YS, Ha, H, Kim, E, Park, Y, Kim, MK, Kwon, DH, Choe, J, Song, HK, Jung, H & Kim, YK 2019, 'eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle', Cell Reports, vol. 26, no. 8, pp. 2126-2139.e9. https://doi.org/10.1016/j.celrep.2019.01.101
Ryu I, Won YS, Ha H, Kim E, Park Y, Kim MK et al. eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. Cell Reports. 2019 Feb 19;26(8):2126-2139.e9. https://doi.org/10.1016/j.celrep.2019.01.101
Ryu, Incheol ; Won, You Sub ; Ha, Hongseok ; Kim, Eunjin ; Park, Yeonkyoung ; Kim, Min Kyung ; Kwon, Do Hoon ; Choe, Junho ; Song, Hyun Kyu ; Jung, Hosung ; Kim, Yoon Ki. / eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle. In: Cell Reports. 2019 ; Vol. 26, No. 8. pp. 2126-2139.e9.
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AB - Exon junction complexes (EJCs) loaded onto spliced mRNAs during splicing serve as molecular markers for various post-transcriptional gene-regulatory processes, including nonsense-mediated mRNA decay (NMD). Although the composition and structure of EJCs are well characterized, the mechanism regulating EJC deposition remains unknown. Here we find that threonine 163 (T163) within the RNA-binding motif of eIF4A3 (a core EJC component) is phosphorylated by cyclin-dependent protein kinases 1 and 2 in a cell cycle-dependent manner. T163 phosphorylation hinders binding of eIF4A3 to spliced mRNAs and other EJC components. Instead, it promotes association of eIF4A3 with CWC22, which guides eIF4A3 to an active spliceosome. These molecular events ensure the fidelity of specific deposition of the EJC ∼20–24 nt upstream of an exon-exon junction. Accordingly, NMD is affected by T163 phosphorylation. Collectively, our data provide evidence that T163 phosphorylation affects EJC formation and, consequently, NMD efficiency in a cell cycle-dependent manner. Ryu et al. show that eIF4A3 (a core EJC component) is phosphorylated at the threonine 163 position by CDK1 and CDK2 in a cell cycle-dependent manner. This event triggers EJC remodeling and affects NMD efficiency in a cell cycle-dependent manner.

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