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In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE118395 | GEO | 2020/07/29

REPOSITORIES: GEO

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In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis [RNAseq/Riboseq]

Project description:Translation is a fundamental biological process, which defines every aspect of cell physiology. Dysregulation of protein synthesis is associated with the diseases, such as ribosomopathies, diabetes, and cancer. To examine translation dysregulation in vivo, we employed RNA interference to knockdown m-subunit of the translation initiation factor eIF3 exclusively in mouse liver. We observed an increase in the number of monosomes and multiple signs of impaired translation. We further characterized the early cellular response using transcriptome sequencing, ribosome profiling, whole proteome, and phosphoproteome analyses. The major response of hepatocytes to eIF3m deficiency was associated with the changes in mRNA expression, with almost no effect on translation efficiency for particular mRNAs. The transcription changes fell into two main categories: ribosome biogenesis (increased transcription of ribosomal proteins, dephosphorylation of eIF2α, and inhibition of rRNA processing) and cell metabolism (lipid, amino acid, nucleic acid, and drug metabolism). Overall, this work uncovers a new mode of regulation of protein synthesis mediated by the inhibition of translation initiation. It also highlights advantages of RNAi-based in vivo approach for studying regulatory network associated with essential factors involved in mammalian translation.

2020-07-29 | GSE120533 | GEO

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (mRNA-seq)

2020-07-29 | GSE118394 | GEO

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (rRNA-seq)

2020-07-29 | GSE118393 | GEO

In Vivo RNAi-Mediated eIF3m Knockdown Affects Ribosome Biogenesis and Transcription but Has Limited Impact on mRNA-Specific Translation.

Project description:Translation is an essential biological process, and dysregulation is associated with a range of diseases including ribosomopathies, diabetes, and cancer. Here, we examine translation dysregulation in vivo using RNAi to knock down the m-subunit of the translation initiation factor eIF3 in the mouse liver. Transcriptome sequencing, ribosome profiling, whole proteome, and phosphoproteome analyses show that eIF3m deficiency leads to the transcriptional response and changes in cellular translation that yield few detectable differences in the translation of particular mRNAs. The transcriptional response fell into two main categories: ribosome biogenesis (increased transcription of ribosomal proteins) and cell metabolism (alterations in lipid, amino acid, nucleic acid, and drug metabolism). Analysis of ribosome biogenesis reveals inhibition of rRNA processing, highlighting decoupling of rRNA synthesis and ribosomal protein gene transcription in response to eIF3m knockdown. Interestingly, a similar reduction in eIF3m protein levels is associated with induction of the mTOR pathway in vitro but not in vivo. Overall, this work highlights the utility of a RNAi-based in vivo approach for studying the regulation of mammalian translation in vivo.

| S-EPMC6926209 | biostudies-literature

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis

Project description:In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis

| PRJNA485434 | ENA

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (mRNA-seq)

Project description:In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (mRNA-seq)

| PRJNA485439 | ENA

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (rRNA-seq)

Project description:In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (rRNA-seq)

| PRJNA485438 | ENA

In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis [RNAseq/Riboseq]

Project description:In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis [RNAseq/Riboseq]

| PRJNA493293 | ENA

Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation.

Project description:Eukaryotic ribosome biogenesis and translation are linked processes that limit the rate of cell growth. Although ribosome biogenesis and translation are mainly controlled by distinct factors, eukaryotic initiation factor 6 (eIF6) has been found to regulate both processes. eIF6 is a necessary protein with a unique anti-association activity, which prevents the interaction of 40S ribosomal subunits with 60S subunits through its binding to 60S ribosomes. In the nucleolus, eIF6 is a component of the pre-ribosomal particles and is required for the biogenesis of 60S subunits, whereas in the cytoplasm it mediates translation downstream from growth factors. The translational activity of eIF6 could be due to its anti-association properties, which are regulated by post-translational modifications; whether this anti-association activity is required for the biogenesis and nuclear export of ribosomes is unknown. eIF6 is necessary for tissue-specific growth and oncogene-driven transformation, and could be a new rate-limiting step for the initiation of translation.

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RbfA and IF3 couple ribosome biogenesis and translation initiation to increase stress tolerance.

Project description:Bacterial ribosome biogenesis and translation occur in the same cellular compartment. Therefore, a biochemical gate-keeping step is required to prevent error-prone immature ribosomes from engaging in protein synthesis. Here, we provide evidence for a previously unknown quality control mechanism in which the abundant ribosome assembly factor, RbfA, suppresses protein synthesis by immature Escherichia coli 30S subunits. After 30S maturation, RbfA is displaced by initiation factor 3 (IF3), which promotes translation initiation. Genetic interactions between RbfA and IF3 show that RbfA release by IF3 is important during logarithmic growth as well as during stress encountered during stationary phase, low nutrition, low temperature, and antibiotics. By gating the transition from 30S biogenesis to translation initiation, RbfA and IF3 maintain the fidelity of bacterial protein synthesis.

| S-EPMC7145577 | biostudies-literature

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