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Global alteration of transcript decay rates upon ZNF598 knockdown

ABSTRACT: We calculated half-life of transcripts in HEK293T cells expressing control or ZNF598-targeting shRNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE233374 | GEO | 2024/07/11

REPOSITORIES: GEO

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Global alteration of transcript decay rates upon ZNF598 knockdown

Project description:Global alteration of transcript decay rates upon ZNF598 knockdown

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Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish [Ribo-seq]

Project description:Quality control of translation is crucial for maintaining cellular and organismal homeostasis. Obstacles in translation elongation induce ribosome collision, which is monitored by multiple sensor mechanisms in eukaryotes. The E3 ubiquitin ligase Znf598 recognizes collided ribosomes, triggering ribosome-associated quality control (RQC) to rescue stalled ribosomes and no-go decay (NGD) to degrade stall-prone mRNAs. However, the impact of RQC and NGD on maintaining the translational homeostasis of endogenous mRNAs has remained unclear. In this study, we investigated the endogenous substrate mRNAs of NGD during the maternal-to-zygotic transition (MZT) of zebrafish development. RNA-Seq analysis of zebrafish znf598 mutant embryos revealed that Znf598 downregulates mRNAs encoding the C2H2-type zinc finger domain (C2H2-ZF) during the MZT. Reporter assays and disome profiling indicated that ribosomes stall and collide while translating tandem C2H2-ZFs, leading to mRNA degradation by Znf598. Our results suggest that NGD maintains the quality of the translatome by mitigating the risk of ribosome collision at the abundantly present C2H2-ZF sequences in the vertebrate genome.

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Project description:mRNA expression profiles were compared between wild-type and ZNF598 knockout cells in the presence or absence of a RIG-I ligand, short poly I:C.

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Project description:Danio rerio znf598, zinc finger protein 598 [Source:NCBI gene;Acc:407728], is differentially expressed in 3 experiment(s);

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Project description:Danio rerio znf598, zinc finger protein 598 [Source:NCBI gene;Acc:407728], is expressed in 1 baseline experiment(s);

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Project description:Xenopus tropicalis znf598, zinc finger protein 598 [Source:Xenbase;Acc:XB-GENE-999290], is differentially expressed in 1 experiment(s);

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