Current research is finding issues with the splicing of mRNA to cancer cells in humans. Some cells are lacking in splicing ability while others are misdirecting the splicing, or over splicing. Why...
Current research is finding issues with the splicing of mRNA to cancer cells in humans. Some cells are lacking in splicing ability while others are misdirecting the splicing, or over splicing. Why may under- or over-splicing cause issues within a eukaryotic cell?
The process of mRNA editing (which includes both capping and splicing) is critical for a cell to produce the correct protein during translation in a ribosome. Geneticists have noticed that the number of protein-encoding regions of DNA can, at times, appear to be too few for a complex organism (such as ourselves). When the human genome project finally came to fruition in the early 2000s, scientists were humbled to find out that the total number of genes that comprise a human was less than 20,000. It was also puzzling that the actual percentage of the genome that would undergo transcription and translation (protein-encoding) was shockingly small, leading us to initially believe that the majority of our DNA was useless. As we delved deeper, it turned out that there is a hierarchy of genes, and the protein-encoding sections were at the bottom of the ladder. Other regions wouldn't necessarily go through protein synthesis but would act as switches that could turn entire segments of DNA on or off, depending on things like environmental factors. This told us that DNA had layers of information that we are just starting to figure out.
The same has been found within protein-encoding regions. Although we initially believed that the segments that were edited out by spliceosomes (introns) were less important than those that were selected to remain (exons--those to be expressed), it turns out it isn't that simple. The intron/exon makeup of a primary transcript (the unedited first run-through of mRNA) is actually quite fluid, and a cell is capable of using or removing the same sections, depending on outside factors. In other words, introns and exons are not set in stone. This nullified the "one gene, one protein" concept. What has remained true is that the exact order of the mRNA nucleotides that make it out of the nucleus is critical for making the correct protein. Protein function is highly dependent on its 3D shape, and any changes to it can have disastrous effects (or beneficial...evolution couldn't happen without these random changes!) on the cell. Considering that cancer results from a misbehaving cell, it comes as no surprise that it can be linked to errors in the editing process. It's sobering to think that it's not just our DNA that is sensitive to changes, but every step along the way to making proteins.
mRNA splicing is very important for the creation of proteins inside a Eukaryotic cell. In a normal cell, messenger RNA or mRNA is created by RNA polymerase from a DNA template inside the nucleus. DNA contains portions of important coded information called exons and "junk" or "filler" called introns used to separate these important genes. Before the mRNA leaves the nucleus to be coded into protein it must first be "cleaned up" so the exact protein can be made. This cleaning process is called splicing. In the case of these cancer cells, over and under splicing of mRNA can be terminal for a eukaryotic cell. This is because proteins are coded very specifically. If there is a single misrepresentation or corruption of even a single base the cell is at risk for making the wrong protein, which in turn can be extremely hazardous for the cell.