DNA ==> RNA ==> Protein

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This post is part of the GRN series. Check out the intro.

This is a very quick and dirty introduction to what biologists call the central dogma:

DNA encodes RNA and RNA encodes proteins.

For thousands of years, people have known that living things pass on traits to their offspring, and we have taken advantage of that for selective breeding of useful organisms – notably clever sheep dogs and big, juicy ears of corn. For many important traits such as size, this is a gradual process, but in the 1850s and 1860s, the botanical experiements of an Austrian named Gregor Mendel established a remarkable fact: heredity is carried in discrete units known as genes. This laid the foundation for our modern understanding: inheritance of quantitative traits such as height, weight, and intelligence is controlled by contributions from many individual genes, but there is no continuous “genetic knob” for them. This post series is about how individual genes are put into action on a molecular level.

Genes are made of a polymer (a repeating molecule) called DNA. It has four subunits, also called “bases” or “nucleotides.” These are (A)denine, (C)ytosine, (G)uanine, and (T)hymine. When the cell wants to use a gene, it first transcribes a copy of the DNA into a very similar substance called RNA. That’s transcription.

DNA is deoxyribonucleic acid and RNA is ribonucleic acid. If you find it hard to parse or remember “deoxyribonucleic acid” or “ribonucleic acid”, consider the root words separately. “Nucleic” means they are found in the nucleus of the cell. “Ribo-“ comes from ribose, a type of sugar that helps the stuff come together. “Deoxy” means the ribose has one oxygen removed. “Acid” is from the fact that DNA is actually acidic in the usual sense.

One the RNA has been transcribed, it then gets moved around, chopped up, and spliced back together. Eventually, it gets used as instructions to make a very different polymer called a protein, which is made out of amino acids. This is called translation. Proteins do most jobs for the cell, controlling cell shape/motion, pH, salt/ion flow, energy production, modifying other proteins, and more. Some proteins bind to DNA and activate or repress transcription, which is important in development and stem cell biology. Those proteins are called transcription factors.

Other important info

  • The quantity of RNA from a gene is a common proxy for activity of that gene: how much is it being transcribed?
  • Some RNAs can already do stuff without ever being used to make protein. These RNAs can operate in many different ways, and they are not completely categorized, but some are called “microRNAs” and others are called “long noncoding RNAs.” They are often harder to measure than regular coding RNAs that code for a protein.
  • Each gene can have multiple isoforms, because the RNA transcript gets spliced (chopped up and mashed back together with different pieces missing). They are not randomly formed or distributed, and they are not interchangeable. Different isoforms are tightly regulated and functionally distinct.
  • Enhancers are pieces of DNA that are not genes, but they help control the activity of nearby genes, often by serving as a landing pad for transcription factors. There are tens of thousands of genes in the human genome, but there are hundreds of thousands of enhancers. Sometimes, the same gene will be active in two similar cell types, but it will be controlled via different enhancers.
  • The way that DNA is packaged (“chromatin state”) is very important for the control of transcription. As a proxy for gene activity, people often measure whether a gene or an enhancer is accessible to DNA chopping enzymes or whether it is packaged with certain chemical modifications called “active marks”. These assays measure chromatin state.
Written on March 10, 2020