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Status |
Public on Apr 25, 2024 |
Title |
Differential expression analysis connects knock-downs of eIF3e and eIF3d with the MAP kinase signaling pathway |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing Other
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Summary |
A prominent hallmark of cancer is deregulated protein synthesis. It is well established that various translation initiation factors (eIFs) are either overexpressed or under-expressed in numerous types of cancer. Recent studies suggest that rather than representing an indirect consequence of neoplasia, imbalanced expression of eIFs significantly contributes to cellular transformation, tumor development, cancer cell survival, metastasis and tumor angiogenesis. Among them, eIF3 stands out as the largest complex composed of 12 subunits with a modular assembly, where aberrant expression of one subunit leads to partially functional subcomplexes. Here we took advantage of well-established knockdowns of subunits d, e and h of human eIF3, all implicated in cancer, and investigated their impact on differential gene expression translatome-wide by Ribo-Seq. We demonstrate that eIF3e and eIF3d knock-downs result in reduced translation efficiency of numerous components of the MAPK signaling pathway, a pathway often upregulated in cancer, and pathways preventing genotoxic stress. Concurrently, depletion of eIF3d increased translation of proteins associated with membrane organelles, whereas eIF3e depletion increased expression of numerous ribosomal proteins, implicating eIF3e in controlling the balanced production of mature ribosomes. Overall, our data illustrate that individual eIF3 subunits exert specific translational control over a broad range of cellular transcripts.
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Overall design |
Ribo-Seq and RNA-Seq data for HeLa cells and its KD derivatives (eIF3d, eIF3e, eIF3h)
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Web link |
https://doi.org/10.7554/eLife.95846.1
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Contributor(s) |
Herrmannová A, Jelínek J, Kerényi F, Pospíšilová K, Wagner S, Brábek J, Valášek LS |
Citation missing |
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Submission date |
Nov 01, 2022 |
Last update date |
Apr 26, 2024 |
Contact name |
Anna Herrmannová |
Organization name |
Institute of Microbiology of the Czech Academy of Sciences
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Lab |
Laboratory of Regulation of Gene Expression
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Street address |
Vídeňská 1083
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City |
Prague |
ZIP/Postal code |
142 20 |
Country |
Czech Republic |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (28)
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GSM6701450 |
Sample 1_HeLa cells, 80S footprints, NT control, rep1 |
GSM6701451 |
Sample 2_HeLa cells, 80S footprints, NT control, rep2 |
GSM6701452 |
Sample 3_HeLa cells, 80S footprints, NT control, rep3 |
GSM6701453 |
Sample 4_HeLa cells, 80S footprints, eIF3d KD, rep1 |
GSM6701454 |
Sample 5_HeLa cells, 80S footprints, eIF3d KD, rep2 |
GSM6701455 |
Sample 6_HeLa cells, 80S footprints, eIF3d KD, rep3 |
GSM6701456 |
Sample 7_HeLa cells, 80S footprints, eIF3e KD, rep1 |
GSM6701457 |
Sample 8_HeLa cells, 80S footprints, eIF3e KD, rep2 |
GSM6701458 |
Sample 9_HeLa cells, 80S footprints, eIF3e KD, rep3 |
GSM6701459 |
Sample 10_HeLa cells, 80S footprints, eIF3h KD, rep1 |
GSM6701460 |
Sample 11_HeLa cells, 80S footprints, eIF3h KD, rep2 |
GSM6701461 |
Sample 12_HeLa cells, 80S footprints, eIF3h KD, rep3 |
GSM6701462 |
Sample 13_HeLa cells, mRNA, NT control, rep1 |
GSM6701463 |
Sample 14_HeLa cells, mRNA, NT control, rep2 |
GSM6701464 |
Sample 15_HeLa cells, mRNA, NT control, rep3 |
GSM6701465 |
Sample 16_HeLa cells, mRNA, NT control, rep4 |
GSM6701466 |
Sample 17_HeLa cells, mRNA, eIF3d KD, rep1 |
GSM6701467 |
Sample 18_HeLa cells, mRNA, eIF3d KD, rep2 |
GSM6701468 |
Sample 19_HeLa cells, mRNA, eIF3d KD, rep3 |
GSM6701469 |
Sample 20_HeLa cells, mRNA, eIF3d KD, rep4 |
GSM6701470 |
Sample 21_HeLa cells, mRNA, eIF3e KD, rep1 |
GSM6701471 |
Sample 22_HeLa cells, mRNA, eIF3e KD, rep2 |
GSM6701472 |
Sample 23_HeLa cells, mRNA, eIF3e KD, rep3 |
GSM6701473 |
Sample 24_HeLa cells, mRNA, eIF3e KD, rep4 |
GSM6701474 |
Sample 25_HeLa cells, mRNA, eIF3h KD, rep1 |
GSM6701475 |
Sample 26_HeLa cells, mRNA, eIF3h KD, rep2 |
GSM6701476 |
Sample 27_HeLa cells, mRNA, eIF3h KD, rep3 |
GSM6701477 |
Sample 28_HeLa cells, mRNA, eIF3h KD, rep4 |
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Relations |
BioProject |
PRJNA896488 |
Supplementary file |
Size |
Download |
File type/resource |
GSE216967_RAW.tar |
2.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
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