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 |
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Sample Preparation:
Sampleprep ID: | SP003308 |
Sampleprep Summary: | Following incubation, the cells were washed with chilled PBS and incubated with 500 µl of extraction solution (80:20 v/v methanol/water) at 4 °C for 5 minutes. Next, cells were scraped with a polypropylene cell scraper and the extraction solution from each sample was collected, vortexed, and incubated on dry ice for at least 30 min. Then, each sample was centrifuged at maximum speed at 4 °C for 10 minutes, and the resulting supernatant was used for metabolic measurements. |