Gene Expression

RNA, Medicine, and the Origins of Life

Blocking transcription and translation is the main action of antibiotics; in addition, the earliest forms of life may have been based on RNA.

Transcription and translation work in a similar fashion in both eukaryotic and prokaryotic cells. However, in prokaryotic cells, the messenger RNA (mRNA) transcript does not undergo posttranscriptional modification and does not require export from the nucleus to the cytoplasm (as prokaryotic cells do not have a nucleus). In prokaryotes, the ribosome often attaches to the free end of the mRNA as the other end is still being transcribed, resulting in transcription and translation happening at the same time on the same RNA strand.

Prokaryotic cells have a different structure from eukaryotic cells. They also undergo transcription and translation slightly differently than eukaryotes do. Antibiotics take advantage of these differences and function to destroy or damage the pathogen through interference with cell wall structure, bacterial transcription, bacterial translation, or all of the above, but they act selectively to target only prokaryotic structures and mechanisms, not eukaryotic ones. Penicillin, for example, specifically attacks the bacterial cell wall, a structure that is absent in animal cells. Fidaxomicin, an antibiotic used to treat Clostridium difficile intestinal infections, blocks the initiation step of RNA synthesis, preventing bacterial transcription. Macrolide antibiotics attack bacterial ribosomes, preventing translation. Although human cells are not vulnerable to these medications, the prokaryotic organisms that make up the human microbiome can be affected, leading to side effects such as gastrointestinal distress or secondary fungal infections.

Before the first prokaryotes arose, the most primitive self-reproducing lifeforms may have consisted entirely of RNA. Like DNA, RNA can encode the message required for building cellular structures (the function of mRNA). However, unlike DNA, RNA has catalytic capacity. Indeed, the ribosome itself is composed mostly of RNA, with a few small proteins involved as well. Because RNA can fold into three-dimensional shapes that afford it specificity, it is thought that RNA may have served as the first structure to both encode instructions for making itself and also provide the catalyst to carry out the process. RNA's ability to self-catalyze has been demonstrated in laboratory conditions. Although it is impossible to know exactly how the simplest forms of life first arose on Earth, the RNA hypothesis is widely accepted.