Grant: Operating Grant

Alternative splicing (AS) is an essential step in the regulation of gene expression and allows a single gene to specify multiple genetic messages (mRNAs) and protein products. Almost all human genes produce mRNAs that undergo AS and it is estimated that this process can result in the expression of orders of magnitude more proteins than there are genes. Alternative splicing is therefore a major process underlying the generation of biological complexity associated with the development and functions of complex metazoan organisms. A major current goal is to understand how AS events are regulated and to determine their biological roles. We have recently discovered the first example of an AS "switch" that is required for the maintenance of embryonic stem cell (ESC) pluripotency and the efficient reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). A major goal of the present application is to identify and characterize additional such AS events such that we have a more complete understanding of the regulation and role of the AS regulatory layer in stem cell biology. This research avenue is expected to provide fundamental new insight into gene regulation, stem cell biology, and it may also yield discoveries that have utility in processes directed at producing iPSCs for therapeutic applications.