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| Status |
Public on Apr 13, 2017 |
| Title |
The 3’-UTR of MYC couples RNA polymerase II function to ribonucleotide levels |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Deregulated expression of MYC enhances glutamine utilization and renders cell survival dependent on an external supply of glutamine, an observation termed “glutamine addiction”. Surprisingly, human colon cancer cells, which express high levels of MYC due to mutations in the WNT pathway, are not glutamine-addicted but undergo a reversible cell cycle arrest upon glutamine deprivation. We show here that glutamine deprivation suppresses endogenous MYC expression via the 3’-UTR of the MYC mRNA, enabling escape from apoptosis. The glutamine-dependent metabolites that mediate this regulation are adenosine nucleotides. Glutamine deprivation causes a global reduction in promoter association of RNA Polymerase II (RNAPII) and reduces the RNAPII traveling ratio, indicative of defects in transcriptional elongation. While RNAPII function is restored by activation of MYC on most genes, restoration of elongation is imperfect and activation of MYC in the absence of glutamine enhances stalling of RNAPII in the body of individual genes, promoting the formation of R-loops. Since stalling of RNAPII and R-loop formation are potential causes of DNA damage, our data argue that the MYC 3’-UTR has a critical role in maintaining genome instability when ribonucleotide levels are low.
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| Overall design |
RNAPII binding in glutamine starved HCT116 cells and ectopic expression of MYC.
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| Contributor(s) |
Dejure FR, Royla N, Herold S, Kalb J, Walz S, Ade CP, Mastrobuoni G, Vanselow J, Schlosser A, Wolf E, Kempa S, Eilers M |
| Citation(s) |
28408437 |
| Submission date |
Sep 07, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Martin Eilers |
| Organization name |
University of Wuerzburg
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| Department |
Chair for Biochemistry and Molecular Biology
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| Lab |
Martin Eilers
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| Street address |
Am Hubland
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| City |
Wuerzburg |
| ZIP/Postal code |
97074 |
| Country |
Germany |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA342303 |
| SRA |
SRP087630 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86556_RAW.tar |
861.2 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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