We propose that the stochastic combination of alternative transcription events has contributed to complex isoform evolution.
Evolutionary interrogation of human biology in well-annotated genomic framework of rhesus macaque.
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View SamplesA genome-wide map of circular RNA in adult zebrafish.
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Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.
Age
View SamplesRibosome stalling during translation has recently been shown to cause neurodegeneration, yet the signaling pathways triggered by stalled elongation complexes are unknown. To investigate these pathways we analyzed the brain of B6J-nmf205-/- mice in which neuronal elongation complexes are stalled at AGA codons due to deficiencies in a tRNA Arg(UCU) tRNA and GTPBP2, a mammalian ribosome rescue factor. Increased levels of phosphorylation of eIF2 (Ser51) were detected prior to neurodegeneration in these mice and transcriptome analysis demonstrated activation of ATF4, a key transcription factor in the integrated stress response (ISR) pathway. Genetic experiments showed that this pathway was activated by the eIF2 kinase, GCN2, in an apparent deacylated tRNA-independent fashion. Further we found that the ISR attenuates neurodegeneration in B6J-nmf205-/- mice, underscoring the importance of cellular and stress context on the outcome of activation of this pathway. These results demonstrate the critical interplay between translation elongation and initiation in regulating neuron survival during cellular stress.
Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation.
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View SamplesRNA-Seq uncovers transcriptomic variations associated with the lethal phenotype conversion on LNCaP progression cell model
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View SamplesTEC (B6 vs Aire KO). Thymic epithelial cells from B6 strain and AIRE KO are compared.
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View SamplesTo find the expression of transfected genes
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View SamplesRNA seq analyses were performed in granulosa cells (GCs) collected from gonadotropin treated ESR2 mutant rats. Data obtained from a null mutant with Esr2 exon 3 deletion (?3) and another DNA binding domain (DBD) mutant with exon 4 deletion (?4) were compared to that of wildtype (WT) rats. The raw data were analyzed using CLC genomics workbench. High quality RNA-sequencing reads were aligned to the Rattus norvegicus genome. Differentially expressed genes in ?3 or ?4 Esr2-mutant GCs were identified based on the following criteria: FDR p-Value =0.05 and an absolute fold change of 2. Fewer differentially expressed genes were identified in ?3 compared to the ?4 mutant group. As both of the mutant groups demonstrated a common phenotype of ovulation failure, differentially expressed genes common to both in ?3 and ?4 mutant rats were emphasized and further analyzed in the companion article “ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation” (Khristi et al., 2018).
ESR2 regulates granulosa cell genes essential for follicle maturation and ovulation.
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View SamplesThe goal of this study was to perform RNA-seq on postnatal day 12 mouse oocytes to quantify gene expression.
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Sex, Specimen part, Disease, Cell line
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Specimen part
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