METTL3 regulates WTAP protein homeostasis

作者：Melissa Sorci, Zaira Ianniello, Sonia Cruciani, Simone Larivera, Lavinia Ceci Ginistrelli, Ernestina Capuano, Marcella Marchioni, Francesco Fazi, Alessandro Fatica · 发表于：Cell Death and Disease · 年份：2018 · DOI：10.1038/s41419-018-0843-z · 被引用次数：137 · 研究领域：RNA modifications and cancer、Cancer-related gene regulation、Epigenetics and DNA Methylation

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 N6-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.