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

Nucleic Acids Research
Kwon JeongYoon Ki Kim

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.

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Citations

Jun 21, 2020·Nature Communications·Yeonkyoung ParkYoon Ki Kim
Nov 5, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Àngels Mateu-ReguéJan Christiansen
Jan 22, 2021·Molecular Therapy. Nucleic Acids·Feng ZhangJinghai Chen
Mar 31, 2021·Autophagy·Jeeyoon ChangYoon Ki Kim
May 22, 2021·Biological Reviews of the Cambridge Philosophical Society·Florence Bonnet-Magnaval, Luc DesGroseillers
Aug 28, 2021·Biomedicines·Hyun Jung HwangYoon Ki Kim

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Datasets Mentioned

BETA
SRP139879

Methods Mentioned

BETA
PCR
PCRs
immunoprecipitation
transfection
pull-down
RNA-IP
reverse-transcription PCR
Assay
Chip
X-ray

Software Mentioned

Bowtie2
QuantSeq
Image J
Bedtools

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis