Technique Maps the Inner Workings of the Nucleolus

Researchers at Princeton have developed a new technique to observe the processes inside the nucleolus, a structure within the cell’s nucleus that plays a key role in building ribosomes. Previously, studying the nucleolus required breaking open the cell, which destroyed much of its structure. Now, with this new method, scientists can track RNA molecules within the nucleolus in living cells, using advanced imaging and genomics techniques. This enables them to watch ribosome assembly as it happens, preserving the cell’s delicate components. 

“These tools give us a window into what’s happening inside the nucleolus in a way we’ve never been able to see before,” explained Clifford Brangwynne, senior author of the study published in Nature. The team now has “a precise spatial and temporal map” of the nucleolus.

The nucleolus consists of three liquid-like layers, each with a distinct role in ribosome assembly. RNA is first produced in the innermost layer and then moves outward, assembling into ribosomal components along the way. Using their mapping technique, researchers tracked how ribosomal RNA moves through these layers, with the smaller subunit assembling mostly in the inner and middle layers, and the larger subunit assembling throughout all three.

Disrupting these processes led to dramatic changes in nucleolar structure, such as layers detaching or even reversing order. The team also created artificial nucleoli to test their findings, discovering that these models functioned similarly to natural ones. Working with collaborators, they found that ribosomal RNA moves from one part of the nucleolus to another only when each processing step is complete, highlighting important quality control checkpoints.

With these new tools, the researchers plan to investigate diseases like cancer, where ribosome production is altered, to identify potential therapeutic targets.