ArticleGenes & development2016
Cap-independent translation by DAP5 controls cell fate decisions in human embryonic stem cells.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 59 citations in OpenAlex.
- Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation.Science advances · 2026Article
- Shifting IRES versus Cap-initiated translation during homeostatic stem cell differentiation and stress.Science advances · 2026Article
- Differentiation stage-specific use of cap-independent and cap-dependent translation initiation in hematopoiesis.bioRxiv : the preprint server for biology · 2025Article
- EIF3D safeguards the homeostasis of key signaling pathways in human primed pluripotency.Science advances · 2025Article
- Review
- Signals from the niche promote distinct modes of translation initiation to control stem cell differentiation and renewal in the Drosophila testis.PLoS biology · 2025Article
- Loss of EIF4G2 mediates aggressiveness in distinct human endometrial cancer subpopulations with poor survival outcome in patients.Oncogene · 2024Article
- Loss-of-function cancer-linked mutations in the EIF4G2 non-canonical translation initiation factor.Life science alliance · 2024Article
- MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression.Journal of orthopaedic surgery and research · 2024Article
- The Roles of eIF4G2 in Leaky Scanning and Reinitiation on the Human Dual-Coding POLG mRNA.International journal of molecular sciences · 2023Article
- Dissecting the roles of EIF4G homologs reveals DAP5 as a modifier of CGG repeat-associated toxicity in a Drosophila model of FXTAS.Neurobiology of disease · 2023Article
- Breast cancer cell mesenchymal transition and metastasis directed by DAP5/eIF3d-mediated selective mRNA translation.Cell reports · 2023Article
- Embryonic poly(A)-binding protein interacts with translation-related proteins and undergoes phosphorylation on the serine, threonine, and tyrosine residues in the mouse oocytes and early embryos.Journal of assisted reproduction and genetics · 2023Article
- Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story.RNA (New York, N.Y.) · 2023Review
- Eukaryotic translation initiation factor eIF4G2 opens novel paths for protein synthesis in development, apoptosis and cell differentiation.Cell proliferation · 2023Review
- RNA degradation eliminates developmental transcripts during murine embryonic stem cell differentiation via CAPRIN1-XRN2.Developmental cell · 2022Article
- DAP5 drives translation of specific mRNA targets with upstream ORFs in human embryonic stem cells.RNA (New York, N.Y.) · 2022Article
- Anomalous HIV-1 RNA, How Cap-Methylation Segregates Viral Transcripts by Form and Function.Viruses · 2022Review
- The mTORC1-eIF4F axis controls paused pluripotency.EMBO reports · 2022Article
- Ribosomal leaky scanning through a translated uORF requires eIF4G2.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple transcriptional and epigenetic changes drive differentiation of embryonic stem cells (ESCs). This study unveils an additional level of gene expression regulation involving noncanonical, cap-independent translation of a select group of mRNAs. This is driven by death-associated protein 5 (DAP5/eIF4G2/NAT1), a translation initiation factor mediating IRES-dependent translation. We found that the DAP5 knockdown from human ESCs (hESCs) resulted in persistence of pluripotent gene expression, delayed induction of differentiation-associated genes in different cell lineages, and defective embryoid body formation. The latter involved improper cellular organization, lack of cavitation, and enhanced mislocalized apoptosis. RNA sequencing of polysome-associated mRNAs identified candidates with reduced translation efficiency in DAP5-depleted hESCs. These were enriched in mitochondrial proteins involved in oxidative respiration, a pathway essential for differentiation, the significance of which was confirmed by the aberrant mitochondrial morphology and decreased oxidative respiratory activity in DAP5 knockdown cells. Further analysis identified the chromatin modifier HMGN3 as a cap-independent DAP5 translation target whose knockdown resulted in defective differentiation. Thus, DAP5-mediated translation of a specific set of proteins is critical for the transition from pluripotency to differentiation, highlighting the importance of cap-independent translation in stem cell fate decisions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.