Current research is linking issues with 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?

mRNA splicing regulates protein expression in eukaryotic cells, so splicing impairments can upset the balance between cell growth and cell death and lead to cancer.

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mRNA splicing is an important step in protein production in eukaryotic cells. When DNA is initially transcribed, this transcript includes both introns and exons. However, introns are not coding regions of DNA and so they need to be spliced out of the transcript. So pre-mRNA splicing removes the introns and leaves the cell with a mature piece of mRNA that can be translated into protein. An interesting aspect of pre-mRNA splicing is that it can be executed in a variety of ways! This is called alternative splicing. When splicing occurs, the cell can also splice out exon sections. This means that multiple mature mRNAs can be derived from a single gene (see attached picture). These alternatively spliced mRNAs each encode for a different protein. Because alternative splicing allows a cell to express multiple proteins from a single gene, it greatly increases the variety of protein a cell is able to express.

So how can splicing errors be related to cancer? Given what we know, take a moment to think about what would happen if a cell was unable to execute any mRNA splicing or if splicing was impaired and so happening less often. If a cell cannot execute any mRNA splicing, it will be unable to produce mature mRNA transcripts that could then be translated into protein. In this situation, cell death would likely ensue. Cancer is considered uncontrolled cell growth and reproduction so it would be unlikely to happen here. But what if splicing is happening inconsistently? In that case, some proteins will be under-expressed because the mRNA transcripts are not consistently receiving the proper splicing. If these proteins are important for regulating cell growth, this could lead to cancer. It's also possible that uncontrolled splicing, or over-splicing, will lead to an abundance of proteins derived from smaller, more spliced mRNA transcripts. If these proteins play a role in cell growth or reproduction, they could also shift the balance toward uncontrolled growth and eventually cancer.

mRNA splicing is an important step in maintaining the necessary abundance of proteins in eukaryotic cells. Impaired or uncontrolled splicing could shift the balance between proteins that promote or regulate cell growth and reproduction. This imbalance could lead to cancer. I have included a link to an article that goes further in depth if you would like to continue learning about this topic! I hope this was helpful!

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