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In vivo RNAi mediated eIF3m knockdown is associated with alterations in ribosome biogenesis and transcription, but has limited mRNA-specific translational effectsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 1 апреля 2020 г.
- Авторы: Smekalova Elena M., Gerashchenko Maxim V., O’Connor Patrick B.F., Whittaker Charles A., Kauffman Kevin J., Fefilova Anna S., Zatsepin Timofei S., Bogorad Roman L., Baranov Pavel V., Langer Robert, Gladyshev Vadim N., Anderson Daniel G., Koteliansky Victor
- Журнал: Molecular therapy. Nucleic acids
- Том: 19
- Год издания: 2020
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- Первая страница: 252
- Последняя страница: 266
- DOI: 10.1016/j.omtn.2019.11.009
- Аннотация: 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.
- Добавил в систему: Зацепин Тимофей Сергеевич