Human population genetic variation and disease causing alterations in microRNA processing
Professor Javier F. Caceres
Secondary Supervisor: Professor Martin Taylor
MicroRNAs are short non-coding RNAs that negatively regulate the expression of target mRNAs, affecting a multitude of cellular pathways. The controlled production of miRNAs is central for cell differentiation and organismal development. We aim to uncover the role of sequence variation in controlling miRNA biogenesis in human populations. We will investigate how individual single nucleotide polymorphisms (SNPs) affect miRNA biogenesis, focusing not only on common genetic variants but also on rare variants associated with human disease, including cancer. We will systematically identify these variants and will study the mechanism by which genetic variation leads to altered expression of these miRNAs.
A change in the sequence of a single miRNA, found in breast and gastric cancer patients, changes the structure and processing of this RNA, leading to more of the mature miRNA being made in the cell. Their data shows that the sequence and structure of RNA molecules are important to control miRNA biogenesis (Fernandez,N (2017) Nat. commun., 8, 15114 | doi: 10.1038/ncomms15114)