Proteins are absolutely essential for the survival of organisms; they carry out many functions that are critical to life. Something needs to build all of those proteins from their basic components. Cells use organelles called ribosomes to accomplish that task. Many ribosomes can work at once to churn out the proteins that are needed using the instructions that are carried on molecules called messenger RNAs. Ribosomes are made up of subunits, which are themselves composed of RNA molecules (ribosomal RNAs) and a variety of proteins. Like proteins, ribosomes also have to be assembled.
Researchers have now learned more about how ribosomes are put together. The work, which utilized cryo-electron microscopy and cryo–electron microscopy, x-ray crystallography to image small subunits as they were used to build a complete ribosome, has been reported in Science.
Researcher Sebastian Klinge, an associate professor and head of the Laboratory of Protein and Nucleic Acid Chemistry at The Rockefeller University, compared the assembly of a ribosome to the construction of origami.
“Segments of RNA and other proteins have to be accurately folded in precise steps. The fundamental problem we are trying to understand is how proteins known as assembly factors work in concert to control each step of the assembly," explained Klinge.
In this work, the researchers used gene editing tools to tag various ribosome assembly factors. They were also able to create a new technique to capture particles that compose the ribosome before they are put together, while they were still in the nucleolus. Those pre-ribosomal particles were imaged at near atomic-level resolution. Interactions between nucleic acids and proteins generated a condensate in the nucleolus, which is an intermediate of the small subunit of the ribosome.
This study followed about 70 different assembly factors that are orchestrated to generate a scaffolding, which is used to construct the small ribosomal subunit and carry it through the path to becoming a ribosome. The assembly factors break apart when the subunit is complete.
While this work has helped us learn more about some aspects of basic biology, it may also be relevant to diseases in which ribosomal components or assembly factors are mutated or disrupted.