An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity

Li, Dan; Yang, Jihong; Malik, Vikas; Huang, Yung‐yu; Huang, Xin; Zhou, Hongwei; Wang, Jianlong

doi:10.1093/nar/gkac1084

Cited by 11 publications

(7 citation statements)

References 79 publications

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“…Eukaryotic initiation factor 4A (EIF4A) family proteins are essential for nuclear export of mRNA (11) and exhibit oncogenes function (12,13). Eukaryotic translation initiation factor 4A3 (EIF4A3) could act as both a classical oncogene and a tumor promotor (14).…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Paired stress granule gene signatures predict survival and inform immune status in hepatocellular carcinoma

Pei

Luo

et al. 2023

Preprint

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Background Stress granules formation is closely associated with the progression of hepatocellular carcinoma (HCC). Factors determination this process remain to be elucidated. In this study, stress granule-related genes were validated as a predictor of HCC. Methods The stress granules-related associated genes were collected from the MSGP database and the MsigDB database. A novel prognostic risk scoring model were constructed by paired gene signature method. We identified eukaryotic translation initiation factor 4A3 (EIF4A3) and karyopherin subunit alpha 2 (KPNA2) as candidate prognostic biomarkers, and their correlation with both prognosis and immune infiltration in HCC were evaluated. The expression of EIF4A3 and KPNA2 in HCC tissues was detected through immunohistochemistry (IHC). Results Through pairing of all DESG gene, we obtained a total of 16251 significance pairs. Subsequently, 93 pairs of all pairs containing EIF4A3 were extracted in this research. As a stress granule formation regulator, KPNA2 displayed the greatest correlations with EIF4A3 in HCC. Hyperactivated EIF4A3 and KPNA2 is associated with the poor clinical outcome of HCCs after hepatic resection. Involvement of EIF4A3 and KPNA2 in immune infiltration have been showed. Conclusion Our study identified coexistence of EIF4A3 and KPNA2 dysregulation inform poor clinical outcomes in HCC.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Paired stress granule gene signatures predict survival and inform immune status in hepatocellular carcinoma

Pei

Luo

et al. 2023

Preprint

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“…One possibility is that EIF4A3, through the EJC, post-transcriptionally controls genes necessary for mitosis progression. For example, in mouse embryonic stem cells (ESCs), EIF4A3 post-transcriptionally controls cell cycle regulators important for pluripotency maintenance (Li et al, 2022). Additionally, EIF4A3 directly binds transcripts encoding the cell cycle regulator Ccnb1 to mediate its nuclear export in ESCs.…”

Section: Discussionmentioning

confidence: 99%

The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis

Lupan

Solecki

Musso

et al. 2023

Preprint

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Mutations in components of the exon junction complex (EJC) are associated with neurodevelopment and disease. In particular, reduced levels of the RNA helicase EIF4A3 cause Richieri-Costa-Pereira Syndrome (RCPS) and CNVs are linked to intellectual disability. Consistent with this, Eif4a3 haploinsufficient mice are microcephalic. Altogether, this implicates EIF4A3 in cortical development; however, the underlying mechanisms are poorly understood. Here, we use mouse and human models to demonstrate that EIF4A3 promotes cortical development by controlling progenitor mitosis, cell fate, and survival. Eif4a3 haploinsufficiency in mice causes extensive cell death and impairs neurogenesis. Using Eif4a3;p53 compound mice, we show that apoptosis is most impactful for early neurogenesis, while additional p53-independent mechanisms contribute to later stages. Live imaging of mouse and human neural progenitors reveals Eif4a3 controls mitosis length, which influences progeny fate and viability. These phenotypes are conserved as cortical organoids derived from RCPS iPSCs exhibit aberrant neurogenesis. Finally, using rescue experiments we show that EIF4A3 controls neuron generation via the EJC. Altogether, our study demonstrates that EIF4A3 mediates neurogenesis by controlling mitosis duration and cell survival, implicating new mechanisms underlying EJC-mediated disorders.

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“…Moreover, a study in recent years unveiled the oncogenic function of EIF4A3 in epithelial ovarian cancer 22 . Apart from the oncogenic role of EIF4A3 in hunman cancers, it is also reported to modulate neurodevelopmental disorders and embryonic stem cell identity 23 , 24 . The comprehensive regulation role of EIF4A3 may be caused by its wide range of effects on gene fate such as m6A suppression, mRNA splicing and RNA-binding protein, implying that spatiotemporal specificity of EIF4A3 RNA may play a critical role in determining and influencing diverse cell fates in disease progression.…”

Section: Discussionmentioning

confidence: 99%

Identification of m6A suppressor EIF4A3 as a novel cancer prognostic and immunotherapy biomarker through bladder cancer clinical data validation and pan-cancer analysis

Yan,

Zhang,

2023

Sci Rep

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EIF4A3 represents a novel m6A suppressor that exerts control over the global m6A mRNA modification level, therefore influencing gene destiny. Despite increasing evidence that highlights a pivotal role of EIF4A3 in tumor progression and immunity, a comprehensive pan-cancer analysis of EIF4A3 has yet to be conducted, in order to ascertain whether EIF4A3 could be a viable biomarker for cancer screening, prediction of prognosis, and to facilitate accurate therapy design in various human malignancies. We analyzed the expression levels of EIF4A3 in bladder cancer compared to para-cancer tissue. Subsequently survival analysis was conducted to ascertain the potential association between EIF4A3 expression and patient prognosis. To further corroborate this evidence, we conducted an extensive data mining process of several publicly available databases, including UCSC Xena database, TCGA, and GTEx. Raw data from the UCSC Xena database was processed using online tools to obtain results that could be subjected to further analysis. Our study unveiled a considerable increase in the expression levels of EIF4A3 in bladder cancer compared to para-cancer tissue. Subsequent validation experiments confirmed that bladder cancer patients exhibiting higher levels of EIF4A3 expression have significantly worse prognostic outcomes. Next, our pan-cancer analysis found that the expression level of EIF4A3 is significantly higher in most cancers. Notably, high expression levels of EIF4A3 were negatively associated with patient prognosis across various cancer types. Furthermore, as a novel m6A suppressor, EIF4A3 was found to be correlated with numerous RNA modification genes in multiple cancer types. Meanwhile, analysis of publicly available databases revealed that EIF4A3 expression was significantly related to immune score and immune cell levels in most cancer types. Interestingly, EIF4A3 was also identified as a superior immunotherapy biomarker when compared to several traditional immunotherapy biomarkers. Lastly, genetic alterations analysis revealed that amplification was the most frequently occurring abnormality in the EIF4A3 gene. EIF4A3 emerges as a promising biomarker with the potential to significantly enhance tumor screening, prognostic evaluation, and the design of individualized treatment strategies across a diverse array of malignancies.

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An RNAi screen of RNA helicases identifies eIF4A3 as a regulator of embryonic stem cell identity

Cited by 11 publications

References 79 publications

WITHDRAWN: Paired stress granule gene signatures predict survival and inform immune status in hepatocellular carcinoma

WITHDRAWN: Paired stress granule gene signatures predict survival and inform immune status in hepatocellular carcinoma

The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis

Identification of m6A suppressor EIF4A3 as a novel cancer prognostic and immunotherapy biomarker through bladder cancer clinical data validation and pan-cancer analysis

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