Ribosomes are highly essential for all cells to prepare the proteins necessary for life. They are the multi-component molecular machines that create complex proteins by binding building blocks together as per instructions encoded in the messenger RNAs of the cell.
Ribosome assembly is an intricate process. The early stages of the assembly, shown above, takes place inside the nucleolus, a structure deep inside the cell’s nucleus. Image Credit: StudioMolekuul/Shutterstock.com
However, ribosomes themselves include small and large subunits, where each subunit is formed of ribosomal proteins and RNA. It is essential for these subunits to be made themselves before they can prepare proteins.
As part of a new study, researchers at the lab of Sebastian Klinge offer the most comprehensive view of how human small ribosomal subunits are assembled by imaging their 3D portraits at three different stages of the assembly process. The study results have been reported in the journal Science.
The assembly of a ribosome is like an 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.”
Sebastian Klinge, Associate Professor and Head, Laboratory of Protein and Nucleic Acid Chemistry, The Rockefeller University
The researchers created a human gene-editing platform for the study to tag ribosome assembly factors. Thus, they devised an innovative biochemical technique to solve the challenge of extracting the pre-ribosomal particles from the nucleolus—a structure found within the cell’s nucleus. Then, they imaged these particles through cryo-electron microscopy, thus unraveling their structure at near-atomic resolution.
The study results explain how around 70 assembly factors congregate to make a scaffolding for building the small subunit, and to guide each step of its maturation. As soon as their work is over, the assembly factors disintegrate and liberate the mature small subunit they held inside.
The study captured three stages that offer better insights into the key molecular mechanisms underlying the formation of the small subunit. The study results also offer a new understanding of rare human diseases caused due to mutations in ribosomal proteins or assembly factors at the time of ribosomal assembly.
Singh, S., et al. (2021) Nucleolar maturation of the human small subunit processome. doi.org/10.1126/science.abj5338.