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| Status |
Public on Jul 07, 2015 |
| Title |
Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Other
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| Summary |
Type-I interferon (IFN)-induced activation of the mammalian target of rapamycin (mTOR) signaling pathway has been implicated in translational control of mRNAs encoding interferon-stimulated genes (ISGs). However, mTOR-sensitive translatomes commonly include mRNAs with a 5’ terminal oligopyrimidine tract (TOP), such as those encoding ribosomal proteins, but not ISGs. Because these translatomes were obtained under conditions when ISG expression is not induced, we examined the mTOR-sensitive translatome in human WISH cells stimulated with IFNβ. The mTOR inhibitor Torin1 resulted in a repression of global protein synthesis, including that of ISG products, and translation of all but 3 ISG mRNAs (TLR3, NT5C3A, and RNF19B) was not selectively more sensitive to mTOR inhibition. Detailed studies of NT5C3A revealed an IFN-induced change in transcription start site resulting in a switch from a non-TOP to a TOP-like transcript variant and mTOR sensitive translation. Thus, we show that, in the cell model used, translation of the vast majority of ISG mRNAs is not selectively sensitive to mTOR activity and describe an uncharacterized mechanism wherein the 5’-UTR of an mRNA is altered in response to a cytokine, resulting in a shift from mTOR-insensitive to mTOR-sensitive translation.
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| Overall design |
WISH cells were induced with interferon in the presence of vehicle, torin-1 or rapamycin. Both polysome-associated and total RNA was analyzed.
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| Contributor(s) |
Larsson O |
| Citation(s) |
26207988 |
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| Submission date |
Jun 25, 2015 |
| Last update date |
Jul 05, 2016 |
| Contact name |
Ola Larsson |
| E-mail(s) |
ola.larsson@ki.se
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| Phone |
+46 (0)8 517 73280
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| Organization name |
Karolinska Institutet
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| Department |
Department of oncology-pathology
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| Street address |
CCK, R8:01
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| City |
Stockholm |
| ZIP/Postal code |
171 76 |
| Country |
Sweden |
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| Platforms (1) |
| GPL18190 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [CDF: Brainarray HuGene11stv1_Hs_ENTREZG_15.1.0] |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA288136 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE70270_RAW.tar |
152.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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