Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs

Kwon Jeong, Incheol Ryu, Joori Park, Hyun Jung Hwang, Hongseok Ha, Yeonkyoung Park, Sang Taek Oh, Yoon Ki Kim

Research output: Contribution to journalArticle

Abstract

Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5'-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC-importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.

Original languageEnglish
Pages (from-to)9313-9328
Number of pages16
JournalNucleic acids research
Volume47
Issue number17
DOIs
Publication statusPublished - 2019 Sep 26

Fingerprint

Karyopherins
RNA Cap-Binding Proteins
Nonsense Mediated mRNA Decay
Messenger RNA
RNA-Binding Proteins
Gene Expression Profiling
Ionizing Radiation
Cytoplasm
Apoptosis
Genes
Proteins

ASJC Scopus subject areas

  • Genetics

Cite this

Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs. / Jeong, Kwon; Ryu, Incheol; Park, Joori; Hwang, Hyun Jung; Ha, Hongseok; Park, Yeonkyoung; Oh, Sang Taek; Kim, Yoon Ki.

In: Nucleic acids research, Vol. 47, No. 17, 26.09.2019, p. 9313-9328.

Research output: Contribution to journalArticle

Jeong, Kwon ; Ryu, Incheol ; Park, Joori ; Hwang, Hyun Jung ; Ha, Hongseok ; Park, Yeonkyoung ; Oh, Sang Taek ; Kim, Yoon Ki. / Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs. In: Nucleic acids research. 2019 ; Vol. 47, No. 17. pp. 9313-9328.
@article{8f44f04a421147549f8637e82847668a,
title = "Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs",
abstract = "Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5'-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC-importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.",
author = "Kwon Jeong and Incheol Ryu and Joori Park and Hwang, {Hyun Jung} and Hongseok Ha and Yeonkyoung Park and Oh, {Sang Taek} and Kim, {Yoon Ki}",
year = "2019",
month = "9",
day = "26",
doi = "10.1093/nar/gkz643",
language = "English",
volume = "47",
pages = "9313--9328",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "17",

}

TY - JOUR

T1 - Staufen1 and UPF1 exert opposite actions on the replacement of the nuclear cap-binding complex by eIF4E at the 5' end of mRNAs

AU - Jeong, Kwon

AU - Ryu, Incheol

AU - Park, Joori

AU - Hwang, Hyun Jung

AU - Ha, Hongseok

AU - Park, Yeonkyoung

AU - Oh, Sang Taek

AU - Kim, Yoon Ki

PY - 2019/9/26

Y1 - 2019/9/26

N2 - Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5'-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC-importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.

AB - Newly synthesized mRNAs are exported from the nucleus to cytoplasm with a 5'-cap structure bound by the nuclear cap-binding complex (CBC). During or after export, the CBC should be properly replaced by cytoplasmic cap-binding protein eIF4E for efficient protein synthesis. Nonetheless, little is known about how the replacement takes place. Here, we show that double-stranded RNA-binding protein staufen1 (STAU1) promotes efficient replacement by facilitating an association between the CBC-importin α complex and importin β. Our transcriptome-wide analyses and artificial tethering experiments also reveal that the replacement occurs more efficiently when an mRNA associates with STAU1. This event is inhibited by a key nonsense-mediated mRNA decay factor, UPF1, which directly interacts with STAU1. Furthermore, we find that cellular apoptosis that is induced by ionizing radiation is accompanied by inhibition of the replacement via increased association between STAU1 and hyperphosphorylated UPF1. Altogether, our data highlight the functional importance of STAU1 and UPF1 in the course of the replacement of the CBC by eIF4E, adding a previously unappreciated layer of post-transcriptional gene regulation.

UR - http://www.scopus.com/inward/record.url?scp=85072508447&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072508447&partnerID=8YFLogxK

U2 - 10.1093/nar/gkz643

DO - 10.1093/nar/gkz643

M3 - Article

C2 - 31361897

AN - SCOPUS:85072508447

VL - 47

SP - 9313

EP - 9328

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 17

ER -