When a cell needs to make a particular protein, it first copies the instructions from the matching gene into a molecule known as a messenger RNA (or an mRNA for short). A simple way to control the level of protein production is to raise or lower the number of these mRNA messages, and living cells have lots of ways to make this happen. One method involves codes built into the mRNAs themselves, called destabilising motifs. These can attract the attention of a group of proteins called Ccr4-Not, which in turn shorten the end of the mRNAs, preparing them for degradation. But how does Ccr4-Not choose which mRNAs to target?
To find out, researchers from Dr Lori Passmore’s group at the MRC Laboratory of Molecular Biology recreated the system in the laboratory using purified molecules. The test-tube system confirmed that a protein called Puf3 forms a bridge between Ccr4-Not and mRNAs. It acts as a tether, recognising a destabilising motif and linking it to Ccr4-Not. Labelling different mRNAs with two colours of fluorescent dye showed how Puf3 helps the cell to choose which to destroy.
Understanding the targets of tethers like Puf3 could help scientists to predict which genes will switch off and when. This could reveal genes that work together, helping to unravel their roles inside cells.
