Gene Splicing Reveals How Human Disease Develops

Kathleen Blanchard's picture

Researchers at Brandeis University and the MRC Laboratory of Molecular Biology in the UK have discovered how gene splicing leads to human disease. The study published Nature, pinpoints exactly where genetic defects that produce 15 to 20 percent of human genetic disorders and disease occur.

The complex process, known as RNA splicing, was observed by the researchers using x-ray crystallography to build a three-dimensional structure consisting of specialized RNA and protein subunits contained with spliceosomes.

The human spliceosome is responsible for relaying genetic material from DNA. Spliceomes send splices of information that promote the formation of proteins, sometimes producing variances that dramatically influence human health.


Lead author and Brandeis biochemist Daniel Pomeranz Krummel explains, "The process of RNA splicing is vital to human cell development and survival. In this process, the regions of our DNA encoding for protein are removed from non-encoding regions and brought together—quite often in alternative arrangements. Defects in this process can have disastrous repercussions in the form of genetic disorders.”

The process of gene splicing identified in the study showed that when one signal from human DNA goes awry the results can lead to human diseases that include epilepsy and other neurological disorders. "In human cells one gene can be made into a variety of proteins, so if the process just goes slightly wrong, the genetic alteration can lead to incredible disaster; yet on the other hand, this incredible complexity has led to our amazing evolutionary progress," says Pomeranz Krummel.

The gene-splicing discovery can tell scientists much about how human disease develops, and should lead to a better understanding of how to prevent and treat disease believed to be the result of genetic disorders. The study is the first to show exactly when genetic encoding produces disease in humans.