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Effects of Triad1-knockdown on ribosome/polysome profiles are reversed by Gcn1-knockdown

ABSTRACT: Previously, we identified ARIH2, the gene encoding Triad1, as a HoxA10 target gene. We found that HoxA10-induced expression of Triad1 was necessary for termination of emergency granulopoiesis, and antagonized leukemogenesis in a murine model of KMT2A-rearranged AML. In this study, we found that knockdown Triad1 increased polysome-specific mRNAs regulating the cellular response to stress, the DNA-damage response, ribosomal biogenesis, or protein catabolism, but decreased mRNAs regulating mitosis, DNA-repair, DNA and RNA metabolism, or Tp53 activity in U937 cells. Polysome-specific mRNAs for Solute Carrier Proteins (SLCs) were also increased by Triad1-knockdown, consistent with correction of metabolic defects during the ISR. This included SLCs involved in import of amino acids, long chain fatty acids and glucose, and lactate export. In comparison of polysome-specific mRNA profiles with Triad1-knockdown versus knockdown of Triad1 plus Gcn1, we identified the same gene and pathway differences as in comparison of Triad1-knockdown to control cells. There were only minor differences in polysome specific mRNAs in cells with Triad1- plus Gcn1-knockdown versus control cells, encompassing fewer differences than with Triad1-knockdown alone. This suggested that Triad1-knockdown on ribosome/polysome profiles are reversed by Gcn1-knockdown in U937 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE284048 | GEO | 2025/01/01

REPOSITORIES: GEO

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Project description:Microarray comparisons of polysome loading in wild-type Arabidopsis and eif3h mutant; Goal: ; To find the target mRNAs that are translationally regulated by eIF3h. BACKGROUND: The eukaryotic translation initiation factor eIF3 has multiple roles during the initiation of translation of cytoplasmic mRNAs. However, the contributions of individual subunits of eIF3 to the translation of specific mRNAs remain poorly understood. RESULTS: Working with stable reporter transgenes in Arabidopsis thaliana it was demonstrated that the h subunit of; eIF3 contributes to the efficient translation initiation of mRNAs harboring upstream open reading frames (uORFs) in their 5â leader sequence. uORFs, which can function as devices for translational regulation, are present in over 30% of Arabidopsis mRNAs, and are enriched among mRNAs for transcriptional regulators and protein modifying enzymes. Microarray comparisons of polysome loading in wild-type and eif3h mutant plants revealed that eIF3h generally helps to maintain efficient polysome loading of mRNAs harboring multiple uORFs. Independently, eIF3h also boosted polysome loading of mRNAs with long coding sequences. Moreover, the lesion in eIF3h revealed a concerted upregulation of translation for specific functional subgroups of mRNAs, including ribosomal proteins and proteins involved in photosynthesis. CONCLUSIONS: The intact eIF3h protein contributes to efficient translation initiation on 5â leader sequences harboring multiple uORFs, although mRNA features independent of uORFs were also implicated. Moreover, our data suggest that regulons of translational control can be revealed by mutations in generic translation initiation factors. Experiment Overall Design: Polysomal and non-polysomal RNA samples were isolated from 10-day-old wild-type and eif3h mutant plants. The translation state (ratio between the polysome and non-polysome, PL/NP) for each gene in the WT and in the mutant was separately established, and then the translation states between the genotype were compared.

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Effects of Triad1-knockdown on ribosome/polysome profiles are reversed by Gcn1-knockdown

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