The human genome contains all the information that a human cell requires to survive and develop healthy and functionally. This information is present in the genome as subunits called genes, which are read by the cell thanks to specialized biological machineries. Genes are first transcribed in the cell nucleus as messenger RNAs (mRNA), which are then exported to the cytoplasm where they are finally translated into proteins. This linear sequence of events is complicated by additional regulatory steps that occur during the process. Indeed, genes are first transcribed as immature precursor mRNAs (pre-mRNAs) that contain both coding (exons) and non-coding segments (introns). In following steps, then, introns are removed and exons are joined together by a process called “splicing” to ultimately obtain a mature mRNA. During splicing, some exons (alternative exons) can be occasionally included from pre-mRNAs, thus generating different mature mRNAs and, as a consequence, different protein isoforms. This process is known as alternative splicing (AS) and it amplifies the protein-coding capacity of the human genome by generating multiple protein isoforms, each with different functions, from a single gene. Alterations during the process of AS can be detrimental for cells, leading to diseases including cancer. Indeed, the identification of mutations in genes coding for AS regulators in tumors highlighted the effects of AS dysfunction in cancer progression.
The aim of this project was to study the physiological mechanism behind alternative splicing of myosin VI in order to understand its de-regulation in tumors and cancer progression.
