Meet the Scientist
Dr. Sujatha Jagannathan
Assistant Professor
Department of Biochemistry and Molecular Genetics
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If DNA is the genetic code that makes you, *you*, then what in the world is RNA?
DNA, or Deoxyribonucleic Acid, is the genetic material in our cells. You can think of our DNA as a cook book filled with instructions (or recipes) to make thousands of proteins that are used to create all of the millions of different cells in our bodies. Think about a classic cookbook, like ‘The Joy of Cooking,’ that contains recipes for all different types of food, ranging from pancakes to pasta to pies. You might be interested in baking an apple pie, so you make a copy of the recipe for apple pie, leaving all the other recipes unused. The copy of the DNA – or recipe – is called RNA, or Ribonucleic Acid. The RNA recipe is transported out of the nucleus and used by machinery in our cells to make proteins.
So why is DNA so important?
DNA is the genetic material that serves as the ultimate user guide (or cook book) for how our bodies work. Because DNA is such a valuable reference, when a cell decides to access and use it, the DNA stays locked and protected within the nucleus. Any messages that leave the nucleus must be taken as notes (or recipes) from the original DNA copy. These messages are in the form of a special type of RNA called messenger RNA or mRNA. These RNA messages carry a copy of the information from the DNA cookbook necessary to make the one protein needed by the cell at that time.
Dr. Sujatha Jagannathan is a scientist at the University of Colorado Anschutz Medical Campus in the Department of Biochemistry and Molecular Genetics who investigates how RNA works and how it is regulated to produce the proteins our bodies need to function.
How does a cell make proteins?
The cells in our body function thanks to thousands of proteins working together to accomplish the tasks needed to keep us going. Different proteins are created when a cell writes down the instructions from DNA into mRNA, which then travels out of the nucleus and into the cytoplasm, where the cellular machinery (called ribosomes) converts the mRNA message into protein. The ribosome reads or translates each line of the RNA message and builds out the basic pieces of a protein – just like adding different ingredients to a recipe. If the recipe calls for two eggs followed by a cup of flour and a pinch of salt, it will add those to the growing protein until the whole recipe has been read. Sometimes, though, the RNA instructions that have been copied from the DNA have errors which can lead to unexpected problems while making the protein. The protein could be too short or contain the wrong ingredients or – worse yet – the cell may fail to make the protein at all.
What causes a ribosome to stop translating RNA into protein?
Errors or mutations in the RNA message can cause the ribosome to stop making protein. These errors are often called ‘nonsense mutations’ that change the original RNA message into nonsense that prematurely tells the ribosome that the message is finished. This is like if the recipe you’re reading for baking a pie told you to add all the ingredients but then only bake it in the oven for 5 minutes. If you followed those instructions, you would be left with an unbaked and inedible pie. Luckily, the cells in our body have a way to recognize when a recipe for proteins has a stop message before the protein is complete; this process is called Nonsense-Mediated RNA Decay, or NMD.
How does Nonsense Mediated Decay (NMD) work?
Nonsense Mediated RNA Decay (NMD) is a process that happens during the end stages of translating the RNA message into protein. In the case of an error-free RNA that contains all the right instructions to make a fully functional protein, the ribosome gets the signals to disengage from the RNA after a job well done and moves on to find a new message to turn into protein. In comparison, when protein production (or translation of the RNA message) is prematurely stopped at a nonsense mutation in the mRNA, there is a ‘window of opportunity’ for NMD factors to assemble around the half-translated mRNA and get rid of it (destroy it!) so that the cell doesn’t try to make more proteins from that same faulty RNA message.
However, if NMD fails to recognize faulty RNA, there are different outcomes depending on why NMD didn’t degrade the faulty RNA. As an example, if there is a premature stop signal that results in the production of a partially formed protein and no NMD process is initiated, the possible results include: 1. a loss of function, like the protein hasn’t even been made; 2. a gain of toxic function, like the protein is working but in a way that causes harm to the cell; or a benign, nonthreatening result that goes unnoticed.
What experiments are Suja and her research team doing to learn more about RNA?
Dr. Jagannathan and her team are focused on learning more about the NMD process with the goal of building a quantitative and predictive model of NMD that can be used in clinical settings for patients with unique genetic variants. The NMD process has been known to the research community for quite a while, but there is still a lot that we don’t understand. Sujatha’s team is currently studying how different cellular factors can influence the timing of NMD and whether they can enhance or slow down the process.
The lab is busy discovering new factors that impact NMD and learning more about how they interact with the RNA message and translating ribosome components. The research from Sujatha’s lab so far has shown that genetic variants that trigger NMD are not always ‘loss of function’ as has been previously believed. The lab is helping clinicians and other researchers understand that not all variants behave in the same way when it comes to NMD, and therefore our understanding of variant-associated diseases requires deeper study.
The lab is busy discovering new factors that impact NMD and learning more about how they interact with the RNA message and translating ribosome components. The research from Sujatha’s lab so far has shown that genetic variants that trigger NMD are not always ‘loss of function’ as has been previously believed. The lab is helping clinicians and other researchers understand that not all variants behave in the same way when it comes to NMD, and therefore our understanding of variant-associated diseases requires deeper study.
FUN FACT: Did you know that Colorado is a hotbed of RNA research activity?!? We even have a Nobel Prize winner who was recognized for his work with RNA!
If you want to learn more about the scientist, please head to their official CU webpage.