Genetics, microRNA and the KRAS-variant
At the heart of genetics is the foundational principle we refer to as the “Central Dogma,” theorized by Francis Crick in 1958 following his contributions toward the discovery of DNA’s structure. The idea traces the flow of genetic information in our cells -- from DNA to RNA to protein. However, as introduced in our previous “Genetics 101” post, new insight into the DNA has led to the discovery of “non-coding RNAs”, parts of the DNA that turn into RNA, but never into protein. This discovery has fundamentally changed our understanding of biology, and has led to discoveries, like the KRAS-variant.
To reiterate, proteins are not always the ultimate destination. DNA can make RNA molecules that never turn into proteins. This new type of RNA is called “non-coding RNA”, meaning that it does not code for a protein product. Rather, it has the much more important job of controlling how our genes and proteins get expressed, and used.
The first discovered class of non-coding RNAs, which are strongly implicated in cancer biology, are microRNAs.
To better understand the role of microRNAs, think about our cells as construction sites. Proteins are the tools that perform vital functions within our cells, like the hammer or the saw, and they are carefully selected based upon the needs of the project. This is where our microRNAs enter the picture. They are the contractors of the project in our cells, overseeing the whole project of cell survival and cell death. MicroRNAs regulate which protein tools are used and when, as well as how much of each are needed. They manage all of the proteins by physically connecting to part of the script for the protein, in a special landing spot, that is found in a region called the 3 prime untranslated region (3’UTR).
MicroRNAs as the contractors in cells
As we have learned more about microRNAs, we now know that they manage much more than single cells, and are used to send signals all over the body, to alert you when there is “danger”, such as an infection, or injury.
Where does the KRAS-variant tie into all of this?
The KRAS-variant is the first example of a broken landing spot of an important microRNA, called let-7, with its key protein target, called KRAS. Having the KRAS-variant is like having a contractor ordering the wrong number of hammers, or the wrong type of saw when work needs to be done.
This can greatly impact how people respond to stresses, like cancer therapy, or even life stresses, like estrogen withdrawal.
This explains why individuals with the KRAS-variant are at risk for certain cancers, and also respond differently to certain cancer treatments, with some working great, and some not as well.
The KRAS-Variant contractor
The discovery of microRNAs, and our work investigating differences in communication pathways between microRNAs and their targets, or the contractors and tools in the cell, provide the foundation for our research at MiraKind, as we set out to hugely advance our understanding of disease risk, prevention, and treatment.