The spliceosome is a molecular machine that plays an important role in gene expression in higher organisms. When the gene is copied into RNA the spliceosome cuts non-coding sequences (introns) out of messenger RNA (mRNA) precursors, and joins together the useful coding sequences (exons) to make continuous protein coding chain. The spliceosome performs this in two steps. First, the start of an intron is recognised, cut, and joined to a specific point in the middle of that intron, forming a lasso-like looped structure. In the second step, the end of the intron is recognised, cut, and the exons joined together. This process called splicing is made more complex in higher organism such as the humans. Different mature mRNAs are produced by joining multiple exons in different combinations. Many different forms of proteins can be produced from a single gene so that proteins can be sent to different parts of the cell or can have silightly different functions. This is called alternative splicing and is crucial in increasing the complexity of the organisms from the limited number of genes. Many human diseases are caused by a failure to remove introns correctly.
Understanding the molecular mechanism of pre-mRNA splicing is very important to understand the cause of many inheritable genetic diseases which is the first step to find cures for these diseases. This will benefit society enormously.
The first important step for the understanding of the mechanism of pre-mRNA is to learn what the spliceosome looks like and to see how it works.
The overall objectives of our project are to biochemically isolate the spliceosome at particular steps of splicing reaction. Making a movie of spliceosome during its action will tell us how the spliceosomes recognise the junction between the exon and intron (splice site) and how it cuts and joins them.
