Summary of Study ST003182
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001981. The data can be accessed directly via it's Project DOI: 10.21228/M8NQ82 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST003182 |
Study Title | METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence |
Study Summary | METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of MTC are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming. |
Institute | University of Texas MD Anderson Cancer Center |
Last Name | Zhang |
First Name | Rugang |
Address | 3SCR3.4121, 1901 East RD, Houston, TX, 77054 |
rzhang11@mdanderson.org | |
Phone | 832-748-6422 |
Submit Date | 2024-04-29 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2024-05-03 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
Analysis ID | AN005226 |
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Analysis type | MS |
Chromatography type | HILIC |
Chromatography system | Thermo Vanquish Horizon UHPLC |
Column | Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um) |
MS Type | ESI |
MS instrument type | Orbitrap |
MS instrument name | Thermo Q Exactive HF-X Orbitrap |
Ion Mode | UNSPECIFIED |
Units | Peak Area |
Chromatography:
Chromatography ID: | CH003953 |
Chromatography Summary: | Hydrophilic interaction liquid chromatography (HILIC) was performed at 0.2 ml/min on a ZIC-pHILIC column (2.1 mm × 150 mm, 5 µm particle size, EMD Millipore) at 45 °C. Solvent A was 20 mM ammonium carbonate, 0.1% ammonium hydroxide, pH 9.2, and solvent B was acetonitrile. The gradient was 85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min. The autosampler was held at 4 °C. For each analysis, 4 µl of sample was injected. |
Instrument Name: | Thermo Vanquish Horizon UHPLC |
Column Name: | Merck SeQuant ZIC-pHILIC (150 x 2.1mm,5um) |
Column Temperature: | 45 |
Flow Gradient: | 85% B for 2 min, 85% B to 20% B over 15 min, 20% B to 85% B over 0.1 min, and 85% B for 8.9 min |
Flow Rate: | 0.2 ml/min |
Solvent A: | 100% water; 20 mM ammonium carbonate; 5 µM medronic acid; 0.1% ammonium hydroxide |
Solvent B: | 100% acetonitrile |
Chromatography Type: | HILIC |