METTL3 regulates WTAP protein homeostasis.
METTL3 regulates WTAP protein homeostasis.
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DOI：
10.1038/s41419-018-0843-z
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发表时间：
2018-07-23
影响因子：
9
通讯作者：
Fatica A
中科院分区：
文献类型：
--
作者：
Sorci M;Ianniello Z;Cruciani S;Larivera S;Ginistrelli LC;Capuano E;Marchioni M;Fazi F;Fatica A
Wilms Tumor 1(WT1)相关蛋白(WTAP)在许多肿瘤中表达上调，包括急性髓系白血病(AML)，它通过与参与RNA加工和细胞增殖的不同蛋白相互作用而发挥致癌作用。此外，WTAP也是N6-甲基腺苷(M6A)沉积到mRNAs所需的核复合体的调节因子，包含METTL3甲基转移酶。然而，目前尚不清楚WTAP是否可能具有m6A独立的调节功能，这可能有助于其致癌作用。在这里，我们证明了METTL3蛋白的下调和过表达都会导致WTAP蛋白的上调，这表明METTL3水平对WTAP蛋白的动态平衡至关重要。然而，我们表明，在缺乏功能性METTL3的情况下，WTAP上调不足以促进细胞增殖。其中，这些数据表明已报道的WTAP的致癌功能严格连接到功能性M6A甲基化复合体。
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.
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