“What the heck do you study in grad school?”

It’s been a busy couple of months for me. We’ve just submitted my first, first-author paper for publication! It has occurred to me that I don’t write much about my personal research, but since I have written a lot about it for this paper (and I really think it is a pretty cool project) I’ve decided it’s time to try to explain a bit about it.

In short, our lab studies Transcription by RNA Polymerase II, which makes protein-coding RNA and regulatory, non-coding RNAs. Most people are already confused when I say this, so here I will try to step back a bit and explain why transcription and RNAs are important.

Most people are somewhat aware of DNA and the fact that it contains genes that somehow determine what color hair you have and if you are more likely to get certain diseases. To have these effects, the DNA of a gene has to be transcribed into RNA, and then the RNA has to be translated into a protein. The protein then performs some function in the cell or body. This overly simplified model has been called “The Central Dogma of Molecular Biology.”

The Central Dogma: The DNA must be replicated and divided evenly between the new cells every time a cell divides. DNA is transcribed into RNA; RNA is translated into protein. Nothing in biology is really this simple, but this is the basic model.

For instance, maybe you have heard about the “gene for breast cancer.” This usually refers to a gene called BRCA1. How does a mutation in BRCA1 cause breast cancer? I’ll use this  gene as a model as we walk through the steps of the Central Dogma.

DNA

BRCA1 is encoded in the DNA, in a code consisting of just four molecules, called nucleotides or bases. The bases in DNA are cytosine (C), thymine (T), adenine (A), guanine (G). These bases pair up A to T, C to G. The specific pattern of A, T, C, and Gs in BRCA1 encode directions to make RNA.

Diagram of the structure of DNA. Guanine “base pairs” with Cytosine, and Adenine base pairs with Thymine (dotted lines in between the blue and red, and green and purple structures.) The phosphate backbone wraps around the outside of these base pairs, giving DNA its famous double helix structure. Creative Commons

RNA

RNA is made up of similar molecules, with a slightly different structure. RNA also has adenine (A), cytosine (C), and guanine (G), but instead of thymine, it has uracil (U). RNA is made by a family of protein complexes called RNA Polymerases. There are three of these family members in eukaryotes (organisms ranging all the way from yeast to humans), each one specializing in RNAs with specific functions. The family member I study, RNA Polymerase II, transcribes RNAs that encode for a protein (as discussed so far) as well as short, non-coding RNAs that have different regulatory functions in the cell (specifically in the nucleus, the organelle that holds the DNA).

A diagram of the organelles in a simplified cell. For this post, focus on 2, 3, and 5. 2 is the nuclease – the home of DNA and transcription. 5 is the ER (endoplasmic reticulum) – the home of ribosomes (3) and translation. Creative Commons

Basically, polymerase travels along the DNA matching up RNA bases to the DNA bases. C and G pair up just like in the DNA, and the RNA U takes the place of the DNA T, so now A and U pair up. This “matching up” takes place as the DNA is threaded through the polymerase. The DNA is “read” by the polymerase which “chooses” the correct RNA base and adds it to the elongating RNA chain.

Video of Transcription:

Protein

After the RNA is transcribed, it is sent out of the nucleus to the endoplasmic reticulum (ER). Here, other molecules called ribosomes translate the RNA into protein. Again, the ribosomes travel along the RNA message, reading the A, U, C, and Gs. Now, three bases are read at a time. These three bases are called a codon, and each codon is a code for a specific amino acid. Each amino acid gets added onto the growing chain, and then the chain gets folded into a functional protein.

Video of Translation:

The properly encoded, transcribed, translated, and folded BRCA1 protein is involved in repair of DNA damage. Our DNA is damaged fairly frequently after exposure to a wide variety of environmental insults, such as UV-rays from the sun and toxins in vehicle exhaust and cigarette smoke. It’s not usually a problem because our cells have proteins such as BRCA1 and other mechanisms to cope with and repair this damage. However, if the DNA encoding the gene for BRCA1 is damaged and not repaired, then the cell may be in trouble. Further DNA damage can accumulate without this repair system, causing de-regulation of the pathways that tell the cell that is doesn’t need to replicate. As cells start to replicate uncontrollably and stop listening to the signals from the rest of the body, they become cancerous. For a number of reasons, Breast and ovarian cells are especially sensitive to mutations in the BRCA1 gene.

For cells to function in any capacity, each step in the central dogma (replication, transcription, and translation) needs to be carefully regulated to ensure that the exact message is communicated quickly and precisely every time. Any disruption of the proteins involved in these steps can lead to cancer, neurological disorders, and developmental issues – if they even support life at all.

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So, I don’t work on all of this. I am specifically studying transcription termination: how polymerase stops making RNA and is released from the DNA at the proper time and location. I will write more specific posts about my work, but I wanted to give a general background first. This type of basic science may not seem as exciting as studying a specific disease like cancer, but it is important to understand the big picture and how a cell should function normally if you want to understand what happens when something goes wrong.

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FOR MORE INFORMATION:

Check out the Genetic Science Learning Center website from the University of Utah. This excellent site is highlighted in my “Resources” page. Their page on “Molecules of Inheritance” has interactive learning tools to help you better understand DNA and genes, RNA, the Central Dogma, and proteins.

You can also check out my Biology & Health Pinterest board. I add cool pictures, infographics, and links about a broad range of topics, including DNA, genetics, and cell biology.

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Title image credit: DNA Strands, Photo by Steve Jurvetson (Flickr, Creative Commons)

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PS. Dear Jason, I am so, so sorry I didn’t talk about histones. Poor, naked DNA. 😦