Genome-wide identification of circular RNAs in eIF4A3 IP
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ABSTRACT:
PROVIDER: PRJNA1001827 | ENA |
REPOSITORIES: ENA
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Project description:RNA helicases are involved in multiple steps of RNA metabolism to direct their roles in gene expression, yet their functions in pluripotency control remain largely unexplored. Starting from an RNAi screen of RNA helicases, we identified that eIF4A3, a DEAD-box (Ddx) helicase component of the exon junction complex (EJC), is essential for the maintenance of embryonic stem cells (ESCs). We mapped the eIF4A3 interactomes in mouse ESCs, revealing that eIF4A3 is widely involved in the post-transcriptional regulation of gene expression. Mechanistically, we show that eIF4A3 post-transcriptionally controls the pluripotency-related cell cycle regulators and that its depletion causes cellular differentiation via cell cycle dysregulation. Specifically, eIF4A3 is required for the efficient nuclear export of Ccnb1 mRNA, which encodes Cyclin B1, a key component of the pluripotency-promoting pathway during cell cycle progression of ESCs. Our results reveal a previously unappreciated role of eIF4A3 and its associated EJC in the post-transcriptional cell cycle control in maintaining stem cell pluripotency.
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Project description:Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Detection of circRNAs from RNA-Seq â triplicate
2015-12-17 | E-GEOD-71195 | biostudies-arrayexpress
Project description:Circular RNAs (circRNAs) are widespread circular forms of non-coding RNAs with largely unknown function. Because stimulation of mammary cells with the epidermal growth factor (EGF) leads to dynamic changes in the abundance of both coding and non-coding RNA molecules, and culminates in the acquisition of a robust migratory phenotype, this cellular model might disclose functions of circRNAs. Here we show that circRNAs of EGF-stimulated mammary cells are stably expressed, while mRNAs and micro-RNAs change within minutes. In general, the circRNAs we detected are relatively long-lived and weakly expressed. Interestingly, they are almost ubiquitously co-expressed with the corresponding linear transcripts, and the respective, shared promoter regions are more active compared to genes producing linear isoforms only. These findings imply that altered abundance of circRNAs, unlike changes in the levels of other RNAs, might not play critical roles in signaling cascades and downstream transcriptional networks that rapidly commit cells to specific outcomes. Histone 3 Lysine 27 Acetylation â 2 replicates
2015-12-17 | E-GEOD-71196 | biostudies-arrayexpress
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Project description:Exon junction complexes (EJCs) deposited on spliced mRNAs play multifunctional roles in the regulation of gene expression. Whereas the formation and components of EJCs are well characterized, the underlying molecular mechanisms for gene regulation remain poorly understood. Here we find that a eukaryotic translation initiation factor (eIF) 4A3, a core component of EJC directly interacts with eIF3g, a subunit of eIF3 complex. This interaction serves as a linker between the EJC and eIF3 complex, consequently driving an internal ribosomal recruitment. Accordingly, artificially tethered EJC component or cellular EJC deposited on mRNA after splicing promotes internal initiation of translation in a way that is resistant to cellular stress induced by serum starvation. We also demonstrate that translatable endogenous or reporter circular RNAs depend on EJC for their association with polysomes. Our results uncover an internal initiation driven by EJC, expanding the protein-coding potential of human transcriptome including circular RNAs.
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