A dividing yeast cell (meshed contour) with aggregates of the ribosomal protein Rpl4 (orange) in the nucleus (blue). Image credit: Benjamin Pillet (CC BY 4.0)
Living cells are packed full of molecules known as proteins, which perform many vital tasks the cells need to survive and grow. Machines called ribosomes inside the cells use template molecules called messenger RNAs (or mRNAs for short) to produce proteins. The newly-made proteins then have to travel to a specific location in the cell to perform their tasks. Some newly-made proteins are prone to forming clumps, so cells have other proteins known as chaperones that ensure these clumps do not form.
The ribosomes themselves are made up of several proteins, some of which are also prone to clumping as they are being produced. To prevent this from happening, cells control how many ribosomal proteins they make, so there are just enough to form the ribosomes the cell needs at any given time. Previous studies found that, in yeast, two ribosomal proteins called Rpl3 and Rpl4 each have their own dedicated chaperone to prevent them from clumping. However, it remained unclear whether these chaperones are also involved in regulating the levels of Rpl3 and Rpl4.
To address this question, Pillet et al. studied both of these dedicated chaperones in yeast cells. The experiments showed that the chaperones bound to their target proteins (either units of Rpl3 or Rpl4) as they were being produced on the ribosomes. This protected the template mRNAs the ribosomes were using to produce these proteins from being destroyed, thus allowing further units of Rpl3 and Rpl4 to be produced. When enough Rpl3 and Rpl4 units were made, there were not enough of the chaperones to bind them all, leaving the mRNA templates unprotected. This led to the destruction of the mRNA templates, which decreased the numbers of Rpl3 and Rpl4 units being produced.
The work of Pillet et al. reveals a feedback mechanism that allows yeast to tightly control the levels of Rpl3 and Rpl4. In the future, these findings may help us understand diseases caused by defects in ribosomal proteins, such as Diamond-Blackfan anemia, and possibly also neurodegenerative diseases caused by clumps of proteins forming in cells. The next step will be to find out whether the mechanism uncovered by Pillet et al. also exists in human and other mammalian cells.
