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.

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Study IDST003182
Study TitleMETTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence
Study SummaryMETTL3 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 NameZhang
First NameRugang
Address3SCR3.4121, 1901 East RD, Houston, TX, 77054
Emailrzhang11@mdanderson.org
Phone832-748-6422
Submit Date2024-04-29
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-05-03
Release Version1
Rugang Zhang Rugang Zhang
https://dx.doi.org/10.21228/M8NQ82
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Sample source
SA346713Pro_2Pro lung embryonic fibroblasts
SA346714Pro_1Pro lung embryonic fibroblasts
SA346715Pro_3Pro lung embryonic fibroblasts
SA346725Sen_shctrl_1Sen_shctrl lung embryonic fibroblasts
SA346726Sen_shctrl_3Sen_shctrl lung embryonic fibroblasts
SA346727Sen_shctrl_2Sen_shctrl lung embryonic fibroblasts
SA346716Sen_shHK2_MutHK2_3Sen_shHK2_MutHK2 lung embryonic fibroblasts
SA346717Sen_shHK2_MutHK2_2Sen_shHK2_MutHK2 lung embryonic fibroblasts
SA346718Sen_shHK2_MutHK2_1Sen_shHK2_MutHK2 lung embryonic fibroblasts
SA346722Sen_shHK2_2Sen_shHK2 lung embryonic fibroblasts
SA346723Sen_shHK2_3Sen_shHK2 lung embryonic fibroblasts
SA346724Sen_shHK2_1Sen_shHK2 lung embryonic fibroblasts
SA346719Sen_shHK2_WTHK2_3Sen_shHK2_WTHK2 lung embryonic fibroblasts
SA346720Sen_shHK2_WTHK2_2Sen_shHK2_WTHK2 lung embryonic fibroblasts
SA346721Sen_shHK2_WTHK2_1Sen_shHK2_WTHK2 lung embryonic fibroblasts
Showing results 1 to 15 of 15
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