1. METTL3 regulates WTAP protein homeostasis.
- Author
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Sorci M, Ianniello Z, Cruciani S, Larivera S, Ginistrelli LC, Capuano E, Marchioni M, Fazi F, and Fatica A
- Subjects
- Cell Cycle Proteins, Cell Line, Tumor, Humans, Leukemia, Myeloid, Acute metabolism, Leukemia, Myeloid, Acute pathology, Methyltransferases antagonists & inhibitors, Methyltransferases genetics, Nuclear Proteins genetics, Proteostasis, RNA Interference, RNA Splicing Factors, RNA, Small Interfering metabolism, Ribosomes metabolism, Methyltransferases metabolism, Nuclear Proteins metabolism
- Abstract
The Wilms tumor 1 (WT1)-associated protein (WTAP) is upregulated in many tumors, including, acute myeloid leukemia (AML), where it plays an oncogenic role by interacting with different proteins involved in RNA processing and cell proliferation. In addition, WTAP is also a regulator of the nuclear complex required for the deposition of N
6 -methyladenosine (m6A) into mRNAs, containing the METTL3 methyltransferase. However, it is not clear if WTAP may have m6A-independent regulatory functions that might contribute to its oncogenic role. Here, we show that both knockdown and overexpression of METTL3 protein results in WTAP protein upregulation, indicating that METTL3 levels are critical for WTAP protein homeostasis. However, we show that WTAP upregulation is not sufficient to promote cell proliferation in the absence of a functional METTL3. Therein, these data indicate that the reported oncogenic function of WTAP is strictly connected to a functional m6A methylation complex.- Published
- 2018
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