Datasets

Title	Dynamic O-GlcNAcylation of eIF3a controls translation reinitiation during integrated stress response
Organism
Number of Samples	20
Release Date	2021/07/28 00:00
Sequencing Types
Protocol Details

Title
Authors	Shu XE,Mao Y,Jia L,Qian SB
Journal	Nature chemical biology
Publication Date	2022 Feb
Abstract	In eukaryotic cells, many messenger RNAs (mRNAs) possess upstream open reading frames (uORFs) in addition to the main coding region. After uORF translation, the ribosome could either recycle at the stop codon or resume scanning for downstream start codons in a process known as reinitiation. Accumulating evidence suggests that some initiation factors, including eukaryotic initiation factor 3 (eIF3), linger on the early elongating ribosome, forming an eIF3-80S complex. Very little is known about how eIF3 is carried along with the 80S during elongation and whether the eIF3-80S association is subject to regulation. Here, we report that eIF3a undergoes dynamic O-linked N-acetylglucosamine (O-GlcNAc) modification in response to nutrient starvation. Stress-induced de-O-GlcNAcylation promotes eIF3 retention on the elongating ribosome and facilitates activating transcription factor 4 (ATF4) reinitiation. Eliminating the modification site from eIF3a via CRISPR genome editing induces ATF4 reinitiation even under the nutrient-rich condition. Our findings illustrate a mechanism in balancing ribosome recycling and reinitiation, thereby linking the nutrient stress response and translational reprogramming. © 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
PMC	PMC8810738
PMID	34887587
DOI

Shu et al. 2021 (PRJNA750456)