A few weeks ago, I saw the new Captain America movie with a few friends. I thoroughly enjoyed all the excitement on the screen, but the 2-hours required to watch a movie does not do justice to all the work that happens behind-the-scenes. This hidden work is absolutely crucial, though viewers are often ignorant about it; a phenomenon that is all too common in the realm of biology.
In my last blog, we explored how certain regions of DNA are transcribed into mRNA and eventually translated into protein. However, just like all the work on a movie set doesn’t appear on the big screen, the vast majority (~98%) of DNA does not actually code for proteins. For many years, these other portions were considered useless (termed “junk DNA”), but we now know that these non-coding regions are vital to ensure proper cellular function.
To understand some of the functions of the other regions, consider the following cinematic analogy: a cell is like a movie director, dictating which protein-- or movie-- gets made. The crew behind the scenes supports the filmmaking process but isn’t necessarily visible in the final product, much like the non-coding portions of DNA support the production of protein.
Just as a book is converted into a movie script and then turned into a movie, a particular gene in the DNA sequence is transcribed into mRNA, which is then translated into a protein. A given gene has certain corresponding sequences in the DNA strand called promoter and repressor elements. These elements work to turn gene transcription on or off respectively. In our analogy, this would be similar to the funding that allows or inhibits a director’s production. A movie that is well funded (i.e. having an active promoter element) can be made with relative ease, especially compared to a movie that is in debt (i.e. having a repressor element).
Some regions of DNA do get transcribed into RNA but are not then translated to protein. For example, tRNAs bring together individual building blocks, or amino acids, to make a functional protein. If we think of these amino acids in the protein like the actors appearing in the film, the tRNA would be like the casting director, determining which actors will star in the movie.
Other RNA species play important regulatory functions. This is loosely analogous to a film editor cutting out unnecessary scenes in the movie. If a particular scene is over exaggerated, it can detract from the quality of the movie. In most superhero movies, the heroes rejoice in saving the world in the last scene. However, if too much attention is drawn to this, it goes from being a heroic finale to a cheesy ending. The film editor has the vital role of ensuring that all the scenes in the movie have a balanced finesse.
In a cell, some RNAs, like microRNAs and long non-coding RNAs, serve these regulatory functions. If too much of a certain gene is transcribed, it throws off the balance required in the cell. Many proteins, when over-produced, can be oncogenic, which means a build-up of such proteins can cause tumor formation. Regulatory RNAs work to ensure that the cell does not produce large quantities of these proteins and instead maintains a healthy balance.
While funders, casting directors, actors, and editors play important roles in filmmaking, there are plenty of other jobs behind-the-scenes. And just as the movie industry can be more complex than described here, the biology is also vastly more complex. These examples represent a small portion of the non-coding sequences which were once known as “junk” DNA, and many parts of the puzzle have yet to be solved. Labs around the world are working to understand the purposes of these other regions. In fact, many regions of non-coding DNA and their corresponding RNAs (if any) may prove to be biomarkers for diseases or even targets for therapy for currently untreatable diseases.
Proteins are fascinating molecules that perform an immense range of functions in the cell. However, their effective production and function are entirely dependent on the non-coding regions of DNA and the molecular network working behind the scenes.