 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jul 29, 2020 |
| Title |
In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis (rRNA-seq) |
| Organism |
Mus musculus |
| Experiment type |
Other
|
| Summary |
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.
|
| |
|
| Overall design |
Total RNAseq experiment comparing 3 replicates of Eif3m knockdown Hepa1c1c7 cells with 3 replicates of control Hepa1c1c7 cells (in vitro samples) and Eif3m knockdown mouse livers with 3 replicates of control mouse livers (in vivo).
|
| |
|
| Contributor(s) |
Smekalova EM, Gerashchenko MV, O'Connor P, Whittaker CA, Bogorad RL, Kauffman K, Fefilova A, Zatsepin T, Gladyshev VN, Baranov PV, Anderson DG, Koteliansky V |
| Citation(s) |
31855834 |
| Submission date |
Aug 10, 2018 |
| Last update date |
Jul 29, 2020 |
| Contact name |
Charles Arthur Whittaker |
| E-mail(s) |
charliew@mit.edu
|
| Organization name |
Koch Institute
|
| Street address |
77 Mass Ave 76-189
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02152 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (12)
|
| GSM3327707 |
d4162: rRNA control in vitro replicate 1 |
| GSM3327708 |
d4163: rRNA control in vitro replicate 2 |
| GSM3327709 |
d4164: rRNA control in vitro replicate 3 |
| GSM3327710 |
d4165: rRNA eIF3m kD in vitro replicate 1 |
| GSM3327711 |
d4166: rRNA eIF3m kD in vitro replicate 2 |
| GSM3327712 |
d4167: rRNA eIF3m kD in vitro replicate 3 |
| GSM3327713 |
d8613: rRNA control in vivo replicate 1 |
| GSM3327714 |
d8614: rRNA control in vivo replicate 2 |
| GSM3327715 |
d8615: rRNA control in vivo replicate 3 |
| GSM3327716 |
d8616: rRNA eIF3m kD in vivo replicate 1 |
| GSM3327717 |
d8617: rRNA eIF3m kD in vivo replicate 2 |
| GSM3327718 |
d8618: rRNA eIF3m kD in vivo replicate 3 |
|
| This SubSeries is part of SuperSeries: |
| GSE118395 |
In vivo RNAi mediated knockdown of translation initiation factor eIF3m is associated with alterations in ribosome biogenesis |
|
| Relations |
| BioProject |
PRJNA485438 |
| SRA |
SRP157046 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE118393_esmekal_rRNA_depths.txt.gz |
361.6 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...