@article{4102,
  keywords = {Animals, Protein Biosynthesis, Mice, Base Sequence, RNA, Messenger, Humans, Models, Biological, Signal Transduction, Cell Proliferation, Male, HEK293 Cells, Cell Cycle Proteins, Cell Line, Tumor, RNA Stability, Mechanistic Target of Rapamycin Complex 1, Adenosine, Eukaryotic Initiation Factors, Proto-Oncogene Proteins c-myc, RNA Splicing Factors, Ribosomal Protein S6 Kinases},
  author = {Sungyun Cho and Gina Lee and Brian Pickering and Cholsoon Jang and Jin Park and Long He and Lavina Mathur and Seung-Soo Kim and Sunhee Jung and Hong-Wen Tang and Sebastien Monette and Joshua Rabinowitz and Norbert Perrimon and Samie Jaffrey and John Blenis},
  title = {mTORC1 promotes cell growth via mA-dependent mRNA degradation.},
  abstract = { <p>Dysregulated mTORC1 signaling alters a wide range of cellular processes, contributing to metabolic disorders and cancer. Defining the molecular details of downstream effectors is thus critical for uncovering selective therapeutic targets. We report that mTORC1 and its downstream kinase S6K enhance eIF4A/4B-mediated translation of Wilms{\textquoteright} tumor 1-associated protein (WTAP), an adaptor for the N-methyladenosine (mA) RNA methyltransferase complex. This regulation is mediated by 5{\textquoteright} UTR of WTAP mRNA that is targeted by eIF4A/4B. Single-nucleotide-resolution mA mapping revealed that MAX dimerization protein 2 (MXD2) mRNA contains mA, and increased mA modification enhances its degradation. WTAP induces cMyc-MAX association by suppressing MXD2 expression, which promotes cMyc transcriptional activity and proliferation of mTORC1-activated cancer cells. These results elucidate a mechanism whereby mTORC1 stimulates oncogenic signaling via mA RNA modification and illuminates the WTAP-MXD2-cMyc axis as a potential therapeutic target for mTORC1-driven cancers.</p> },
  year = {2021},
  journal = {Mol Cell},
  volume = {81},
  pages = {2064-2075.e8},
  month = {2021 May 20},
  issn = {1097-4164},
  doi = {10.1016/j.molcel.2021.03.010},
  language = {eng},
}