When the gene product of these mutations is lost or inactivated, the cells die, but in the process, the roll of the gene in question is also revealed. The Tollervey group also uses other genetic techniques to study where proteins locate within the cell, performing experiments in which a selected protein is fused to a small tag sequence that can be traced. Similar methods can be used to pull the protein or any complex of which it is a component from extracts of cells. Armed with such techniques, the group has dissected the pathway of ribosome synthesis. In eukaryotic cells, ribosome synthesis occurs in a specialised compartment of the nucleus called the nucleolus.
Nucleolar research has a long history.
Nucleoli were first discovered in Viper venom by Fontana in 1781. By the end of the 19th century, it was already clear that nucleoli are present within the nucleus in all cell types and that they are dynamic, active structures. During the early 20th century, scientists recognised that ribosomes are synthesised in the nucleoli and are then transported to the cytoplasm, where they construct all the proteins of the cell. The ribosomal RNAs and rDNA were at the forefront of molecular biology, being the first RNAs and DNAs to be characterised and then sequenced. During the late 1970s the rDNAs were sequenced from several organisms, including yeast and humans, and the basic steps in the pre-rRNA processing pathways were worked out.