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eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle

Title
eIF4A3 Phosphorylation by CDKs Affects NMD during the Cell Cycle
Author
최준호
Keywords
EXON JUNCTION COMPLEX; MESSENGER-RNA DECAY; ENHANCES TRANSLATION; CRYSTAL-STRUCTURE; MAMMALIAN-CELLS; PROTEIN; REVEALS; IDENTIFICATION; CORE; SEQ
Issue Date
2019-02
Publisher
CELL PRESS
Citation
CELL REPORTS, v. 26, NO 8, Page. 2126-2126
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-dependentmanner. 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 similar to 20-24 nt up-stream 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.
URI
https://www.sciencedirect.com/science/article/pii/S221112471930138X?via%3Dihubhttp://repository.hanyang.ac.kr/handle/20.500.11754/107487
ISSN
2211-1247
DOI
10.1016/j.celrep.2019.01.101
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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