The role of the RNA methyltransferase complex in transcriptional regulation and cancer

有必要了解正常的细胞和分子过程，以便开发新的诊断和治疗方法，以应对我们老龄化社会面临的医疗保健挑战。一个非常感兴趣的领域涉及RNA m6A甲基化在正常细胞功能和疾病中的作用。动态RNA甲基化被认为是由添加（胃L3和胃L14）或去除（FTO和ALKBH 5）甲基的蛋白质介导的。我们和其他人已经确定了胃L3在基因调控和剪接中的作用，但是对胃L14的确切功能作用仍然知之甚少。此外，直到现在才认识到胃L3和胃L14在各种致病过程中的潜在作用。在本项目中，我们将详细分析胃L3和胃L14在类固醇激素介导的基因调控中的作用。类固醇激素，如雄激素、雌激素和孕酮，在青春期发育、生殖和某些癌症中起重要作用。这些类固醇激素通过核受体起作用，调节靶基因的表达。在这里，我们将评估的RNA甲基转移酶复合物在雌激素和雄激素反应细胞系的功能，并将使用多学科的方法来确定的分子和表型功能的不同组成部分的RNA甲基转移酶复合物在类固醇激素信号转导。

It is necessary to understand normal cellular and molecular processes to enable new diagnostics and treatments to be developed to address the health care challenges which face our aging society. One area of intense interest relates to the role of RNA m6A methylation in normal cellular functions and disease. Dynamic RNA methylation is believed to be mediated by proteins which add (METTL3 and METTL14) or remove (FTO and ALKBH5) methyl groups. We and others have defined roles for METTL3 in gene regulation and splicing, however the exact functional roles of METTL14 remain poorly understood. Furthermore, the potential role of METTL3 and METTL14 in a variety of pathogenic processes is only now being recognized. In this project we will dissect the roles of METTL3 and METTL14 in steroid hormone mediated gene regulation. Steroid hormones, such as androgens, estrogens and progesterone, play important roles in pubertal development, reproduction and certain cancers. These steroid hormones, acting via nuclear receptors, regulate expression of target genes. Here we will assess the function of the RNA methyltransferase complex in estrogen and androgen responsive cell lines and will use a multidisciplinary approach to determine the molecular and phenotypic functions of the distinct components of the RNA methyltransferase complex in steroid hormone signaling.