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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Collection:
| Collection ID: | CO003294 |
| Collection Summary: | IMR90 primary human diploid lung embryonic fibroblasts were used and cultured in DMEM medium supplemented with 10% fetal bovine serum (FBS), L-glutamine, sodium pyruvate, non-essential amino acids, sodium bicarbonate and 1% penicillin-streptomycin under low oxygen tension (2%). |
| Sample Type: | Cultured cells |
