OK. I admit it. My bio-crushes are sometimes weird. Two years ago I was obsessed with the tiny African killifish, and earlier this year I was extolling the virtues of the laboratory roundworm. Now, thanks to geneticist and developmental biologist Maria Barna, PhD, I only have eyes for the ribosome. Tens of thousands of these tiny cellular machines birth proteins based on instructions encoded on messenger RNAs, which ferry a gene's genetic code from the DNA in the nucleus into the cell's cytoplasm. This army of ribosomes (each made up of about 80 core proteins) is critically important to the life of a cell. As such, individual ribosomes have been thought to be interchangeable and relatively mindless, obediently "translating" any and all nearby messenger RNAs.
Now Barna, who is a New York Stem Cell Robertson Investigator, and postdoctoral scholars Zhen Shi, PhD, Kotaro Fujii, PhD, and Deniz Simsek, PhD, have turned this notion on its head by showing that ribosomes differ in their core protein components and in the complement of associated proteins that hang off their outer shells. Contrary to what's been taught in countless basic biology textbooks and classes, these differences lead to ribosomes with specific preferences. Some appear to prefer to translate proteins associated with cellular metabolism; others focus on proteins important in embryonic development.
The implications of their research, published their results in a pair of papers, one in Cell earlier this month and one today in Molecular Cell, are both confounding and astounding. As I described in our release:
The [research] highlights a way that a cell could transform its protein landscape by simply modifying ribosomes so that they prefer to translate one type of gene — say, those involved in metabolism — over others. This possibility would free the cell from having to micromanage the expression levels of hundreds or thousands of genes involved in individual pathways. In this scenario, many more messenger RNAs could be available than get translated into proteins, simply based on what the majority of ribosomes prefer, and this preference could be tuned by a change in expression of just a few ribosomal proteins.
This discovery was completely unexpected. These findings will likely change the dogma for how the genetic code is translated. Until now, each of the 1 to 10 million ribosomes within a cell has been thought to be identical and interchangeable. Now we’re uncovering a new layer of control to gene expression that will have broad implications for basic science and human disease.
I'm smitten by this idea that ribosomes have unexpected depths that could fundamentally alter our perception of how cells control the regulation of their genes. There's something so satisfying about the idea of discovering something new under our very eyes.
Unfortunately, however, my new crush isn't much to look at on paper. Instead I give you this fantastic, 80-foot-long sculpture at Cold Spring Harbor Laboratories in New York. It's called "Waltz of the Polypeptides", by Mara G. Haseltine. It depicts ribosomes at work translating a protein (the tangly, spaghetti-looking thing) based on the long messenger RNA (the straightish pipe along which the ribosomes are traveling). Look how lovingly the two ribosomal subunits cradle their newborn protein! It's almost too much.