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

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.