Protein complex formation as a rationale for translation factories

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The information encoded in genes in living cells is decoded to produce chains of amino acids called proteins, which fold up to form functional and mature forms. The complement of mature proteins present in a cell dictate its identity, function and health. Proteins carry out most biological functions, catalyzing biochemical reactions as well as serving structural and regulatory roles. Most of these functions involve proteins acting in concert with other proteins, frequently in so-called molecular machines where different protein subunits come together to form complexes. This provides enormous flexibility and control, and cells devote large resources to making these complexes in all organisms from bacteria to man. When it goes wrong and protein complex assembly goes awry, this has wide ranging implications. For example, it is known that protein interaction surfaces are hot-spots for many human genetic disease-associated mutations.Estimates suggest that in yeast cells there are up to 60 million protein molecules per cell, whereas in a human cell this number rises to over 10 billion, and roughly half of these protein molecules in each system form part of protein complexes. The inherent complexity in producing so many molecular machines raises a key question: how do individual protein molecules within this protein sea find their correct, cognate partner(s) and form appropriate protein complexes? Given that each protein molecule is synthesized independently, using a template molecule, mRNA, it is not immediately obvious how cells solve this 'needle in a haystack' problem. However, recent evidence has shown a simple solution to this challenge is to ensure that the different proteins from the same complex are synthesized in the same defined subcellular location. This can be viewed as a factory, which specializes in making selected protein complexes. In order to achieve this, the cell factory model benefits from colocalizing the template mRNA molecules to the same locale. In this proposal, we will use the yeast cell due to its relative simplicity, and the range of reagents available to resolve a number of key questions linked to this model. We will determine how widespread this factory-associated assembly of protein complexes is, how the factories form and are regulated, and how important the factory-mediated assembly of protein complexes is for a cell's life.