Mechanisms of METTL3 in breast cancer and metastasis

Similar to DNA and proteins, RNA can be post-transcriptionally modified by a wide range of chemical marks.

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic messenger RNA (mRNA) and has emerged as a crucial mechanism for regulation of gene expression. m6A is a dynamic modification, deposited by ‘writers’, being METTL3 the catalytically active subunit, removed by ‘erasers’ and decoded by ‘readers’ that dictate the molecular impact of the m6A-modified mRNA.

Alterations in those regulatory proteins are causative of many human diseases including cancer.Objective: To establish the function of m6A modifications and METTL3 activity, by systematically characterizing the biological impact of m6A-modified mRNAs and by elucidating novel functional interactions of METTL3.Methods: We will employ several cancer models with a focus on breast cancer.

We will use a progressive approach from classical biochemistry and molecular tools to mouse and clinical models, combined with multiple layers of high-throughput analysis.Importance: These studies will significantly advance our understanding of RNA modifications and their role in breast cancer development and metastasis.

In addition, the results of this project will stimulate a wider understanding of the role of RNA modifications in regulating gene expression in other human cancers, which will facilitate the development of better diagnostics and novel therapies.