Roiuk et al. 2024 (PRJNA1019669)

General Details

Title	eIF4E-independent translation is largely eIF3d-dependent
Organism
Number of Samples	4
Release Date	2023/09/21 00:00
Sequencing Types
Protocol Details

Study Links

GWIPS-viz	Trips-Viz

Repository Details

SRA	SRP462456
ENA	SRP462456
GEO	0.0
BioProject	PRJNA1019669

Publication

Title
Authors	Roiuk M, Neff M, Teleman AA
Journal	Nature communications
Publication Date	2024 Aug 6
Abstract	Translation initiation is a highly regulated step needed for protein synthesis. Most cell-based mechanistic work on translation initiation has been done using non-stressed cells growing in medium with sufficient nutrients and oxygen. This has yielded our current understanding of 'canonical' translation initiation, involving recognition of the mRNA cap by eIF4E1 followed by successive recruitment of initiation factors and the ribosome. Many cells, however, such as tumor cells, are exposed to stresses such as hypoxia, low nutrients or proteotoxic stress. This leads to inactivation of mTORC1 and thereby inactivation of eIF4E1. Hence the question arises how cells translate mRNAs under such stress conditions. We study here how mRNAs are translated in an eIF4E1-independent manner by blocking eIF4E1 using a constitutively active version of eIF4E-binding protein (4E-BP). Via ribosome profiling we identify a subset of mRNAs that are still efficiently translated when eIF4E1 is inactive. We find that these mRNAs preferentially release eIF4E1 when eIF4E1 is inactive and bind instead to eIF3d via its cap-binding pocket. eIF3d then enables these mRNAs to be efficiently translated due to its cap-binding activity. In sum, our work identifies eIF3d-dependent translation as a major mechanism enabling mRNA translation in an eIF4E-independent manner. © 2024. The Author(s).
PMC	PMC11303786
PMID	39107322
DOI

	Run Accession	Study Accession	Scientific Name	Cell Line	Library Type	Treatment	GWIPS-viz	Trips-Viz	Reads	BAM	BigWig (F)	BigWig (R)
	SRR26132850	PRJNA1019669	Homo sapiens	HeLa	0.0	0.0
	SRR26132849	PRJNA1019669	Homo sapiens	HeLa	0.0	0.0
	SRR26132848	PRJNA1019669	Homo sapiens	HeLa	0.0	0.0
	SRR26132851	PRJNA1019669	Homo sapiens	HeLa	0.0	0.0
	Run Accession	Study Accession	Scientific Name	Cell Line	Library Type	Treatment	GWIPS-viz	Trips-Viz	Reads	BAM	BigWig (F)	BigWig (R)

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