In Vivo RNAi-Mediated eIF3m Knockdown Affects Ribosome Biogenesis and Transcription but Has Limited Impact on mRNA-Specific Translation.
eIF3
eIF3m
in vivo
liver
mTOR
rRNA
ribosomal genes
ribosome profiling
siRNA
translation
Journal
Molecular therapy. Nucleic acids
ISSN: 2162-2531
Titre abrégé: Mol Ther Nucleic Acids
Pays: United States
ID NLM: 101581621
Informations de publication
Date de publication:
06 Mar 2020
06 Mar 2020
Historique:
received:
03
06
2019
revised:
20
10
2019
accepted:
05
11
2019
pubmed:
20
12
2019
medline:
20
12
2019
entrez:
20
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31855834
pii: S2162-2531(19)30362-2
doi: 10.1016/j.omtn.2019.11.009
pmc: PMC6926209
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
252-266Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK117149
Pays : United States
Informations de copyright
Published by Elsevier Inc.
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