Summary of project PR001981

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

Project ID: PR001981
Project DOI:doi: 10.21228/M8NQ82
Project Title:METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence
Project 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
Email:rzhang11@mdanderson.org
Phone:832-748-6422

Summary of all studies in project PR001981

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
Release
Date
VersionSamplesDownload
(* : Contains raw data)
ST003182 METTL3-mediated chromatin contacts promote stress granule phase separation through metabolic reprogramming during senescence Homo sapiens University of Texas MD Anderson Cancer Center MS 2024-05-03 1 15 Uploaded data (3.5G)*
  logo