Background |
A major focus of the work
in my lab is to understand one of the most fundamental problems in
molecular biology today: how do organisms regulate the expression
of their genetic material? In particular, our work examines the role
of pre-mRNA splicing in this process. Because the coding regions of
most eukaryotic genes are interrupted by non-coding introns, appropriate
expression of these genes requires the precise removal of their introns
in a process catalyzed by the spliceosome. While the presence of introns
in eukaryotic genes has been known for over three decades, the importance
of pre-mRNA splicing in the gene expression pathway has been reinforced
by the sequencing of the human genome. While many were initially surprised
by the relatively small number of genes encoded in our genome, it
soon became clear that a significant amount of genomic diversity could
be generated by changing the order in which the coding regions of
many genes are spliced together – a process termed alternative
splicing (reviewed in Black Cell 2000; Blencowe Cell 2006).
Indeed, the average human gene is interrupted by eight introns (Lander,
et al. Nature 2001), and it is now clear that the splicing
patterns for many genes change in different cell types and under different
developmental conditions. The importance of pre-mRNA splicing and
its appropriate regulation has been further augmented over the past
few years by the number of disease states that have been associated
with its mis-regulation (reviewed in Faustino and Cooper, Genes
Dev 2003). While these examples make clear the importance of the
process of alternative splicing, remarkably little is currently known
about the capacity of the spliceosome to function as a regulatory
control point in the gene expression pathway. |
