RNA processing and human disease

Gene expression involves multiple regulated steps leading from gene to acti ve protein. Many of these steps involve some aspect of RNA processing. Dise ases caused by mutations that directly affect RNA processing are relatively rare compared with mutations that disrupt protein function. The vast major ity of diseases of RNA processing result from loss of function of a single gene due to mutations in cis-acting elements required for pre-messenger RNA (mRNA) splicing. However, a few diseases are caused by alterations in the trans-acting factors required for RNA processing and in the vast majority o f cases it is the pre-mRNA splicing machinery that is affected. Clearly, al terations that disrupt splicing of pre-mRNAs from large numbers of genes wo uld be lethal at the cellular level. A common theme among these diseases is that only subsets of genes are affected. This is consistent with an emergi ng view that different subsets of exons require different sets of cis-actin g elements and trans-acting factors.