Grant: CIHR Fellowship

Nucleic acids, such as DNA and RNA, have fundamental roles as carriers of genetic information. Genes encoded in DNA are transcribed into RNA molecules and subsequently translated into proteins, the effectors that mediate biological activities. Cancer cells undergo vast changes in gene expression that enable uncontrolled growth and increased cellular division. Untranslated regions of messenger RNAs play a crucial role in controlling these changes. In many cancers, these regions are dramatically shortened, and normal gene regulation is abolished. Yet, we still do not fully understand how cancer cells choose and regulate the length of the untranslated regions. Messenger RNAs additionally undergo diverse types of chemical modifications in cells. One such modification, the recently discovered methylation of adenines (N6-methyladenosine), was proposed to control the length of the untranslated regions of some RNAs. Interestingly, the proteins that are responsible for N6-methyladenosine are altered in lymphomas, brain and breast cancers. Thus, it could be an important mechanism by which cancer cells modulate the expression of disease-promoting genes. This project will investigate the link between the N6-methyladenosine RNA modification and the control of gene expression in breast cancer cells. Using molecular and biochemical approaches, we will remove N6-methyladenosines and measure the changes in expression of cancer-relevant genes. This work will help to better establish how cancer cells regulate gene expression at a fundamental level, with the hope that this knowledge can help us devise better and more effective treatments in the future.