ArticleRNA (New York, N.Y.)2022
DAP5 drives translation of specific mRNA targets with upstream ORFs in human embryonic stem cells.
Article in RNA (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Real-time single-molecule imaging in zebrafish embryos uncovers noncanonical translation.Science advances · 2026Article
- Eukaryotic translation initiation factor 4F: functional properties and physiological role.Nucleic acids research · 2025Review
- Specialized ribosomes: integrating new insights and current challenges.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- The Flipons, Infections, and Amyloids that Foreshadow the Fading Memories of Alzheimer's Disease.Neuroscience insights · 2025Review
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- Ribosome rescue factor PELOTA modulates translation start site choice for C/EBPα protein isoforms.Life science alliance · 2024Article
- Upstream open reading frames: new players in the landscape of cancer gene regulation.NAR cancer · 2024Review
- 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
- RNA-binding protein Nocte regulates Drosophila development by promoting translation reinitiation on mRNAs with long upstream open reading frames.Nucleic acids research · 2024Article
- Neurodegenerative diseases reflect the reciprocal roles played by retroelements in regulating memory and immunity.Frontiers in neuroscience · 2024Article
- The Roles of eIF4G2 in Leaky Scanning and Reinitiation on the Human Dual-Coding POLG mRNA.International journal of molecular sciences · 2023Article
- mTOR inhibition reprograms cellular proteostasis by regulating eIF3D-mediated selective mRNA translation and promotes cell phenotype switching.Cell reports · 2023Article
- PRRC2 proteins impact translation initiation by promoting leaky scanning.Nucleic acids research · 2023Article
- Specific mechanisms of translation initiation in higher eukaryotes: the eIF4G2 story.RNA (New York, N.Y.) · 2023Review
- To initiate or not to initiate: A critical assessment of eIF2A, eIF2D, and MCT-1·DENR to deliver initiator tRNA to ribosomes.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death associated protein 5 (DAP5/eIF4G2/NAT1) is a member of the eIF4G translation initiation factors that has been shown to mediate noncanonical and/or cap-independent translation. It is essential for embryonic development and for differentiation of embryonic stem cells (ESCs), specifically its ability to drive translation of specific target mRNAs. In order to expand the repertoire of DAP5 target mRNAs, we compared ribosome profiles in control and DAP5 knockdown (KD) human ESCs (hESCs) to identify mRNAs with decreased ribosomal occupancy upon DAP5 silencing. A cohort of 68 genes showed decreased translation efficiency in DAP5 KD cells. Mass spectrometry confirmed decreased protein abundance of a significant portion of these targets. Among these was KMT2D, a histone methylase previously shown to be essential for ESC differentiation and embryonic development. We found that nearly half of the cohort of DAP5 target mRNAs displaying reduced translation efficiency of their main coding sequences upon DAP5 KD contained upstream open reading frames (uORFs) that are actively translated independently of DAP5. This is consistent with previously suggested mechanisms by which DAP5 mediates leaky scanning through uORFs and/or reinitiation at the main coding sequence. Crosslinking protein-RNA immunoprecipitation experiments indicated that a significant subset of DAP5 mRNA targets bound DAP5, indicating that direct binding between DAP5 protein and its target mRNAs is a frequent but not absolute requirement for DAP5-dependent translation of the main coding sequence. Thus, we have extended DAP5's function in translation of specific mRNAs in hESCs by a mechanism allowing translation of the main coding sequence following upstream translation of short ORFs.
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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.