Frog eggs without a nucleolus revealed the cell's ribosome factory
In 1964 John Gurdon and Donald Brown noticed that a quarter of their clawed-frog eggs had no nucleolus, and none of those eggs survived. Two years later hybridisation experiments showed why: the DNA packed inside that dense blob inside the nucleus holds the code for ribosomal RNA, the backbone of every protein-making machine.
No structure inside the nucleus of a eukaryotic cell is bigger than the nucleolus. It was spotted by microscope in the 1830s, and in 1839 Theodor Schwann described small bodies that Matthias Schleiden had found inside nuclei, calling them by a German word meaning nucleus-corpuscle. For more than a century its purpose stayed murky. The frog study, in which half the eggs had one nucleolus and a quarter had two, established that it was essential, and Max Birnstiel's team in 1966 tied it to ribosomal RNA genes.
In higher organisms it has three zones. Ribosomal DNA is transcribed in a fibrillar centre, a dense fibrillar layer holding the protein fibrillarin processes the RNA, and a granular outer part completes assembly. Polymerase I copies most ribosomal RNA as one long precursor, which small guide RNAs help trim and modify into three pieces. A fourth piece is made elsewhere in the nucleus by polymerase III and imported, along with ribosomal proteins built out in the cytoplasm and brought back. The finished small and large subunits then leave through nuclear pores.
Although a typical view shows one or two, a diploid human cell carries ten chromosome regions that can organise nucleoli. Plant nucleoli often have a clear central vacuole and, unlike animal ones, hold very high levels of iron.
The nucleolus does more than build ribosomes. It helps form signal recognition particles, responds to stress and can trap particular proteins so they cannot reach their partners, a control process called nucleolar detention driven by long noncoding RNAs. Faults in it underlie human disorders called nucleolopathies, and researchers are studying it as a target for cancer drugs.
Source: Nucleolus
