Gene Machine: The Race to Decipher the Secrets of the Ribosome

by Venki Ramakrishnan

Jonathan figured that with new sequencing techniques you could break open a cell, chew up all the RNA, and then take the pieces of mRNA protected by the different ribosomes in the cell, amplify them, and sequence them. You would then get a snapshot of what ribosomes were doing on every region of every mRNA at a particular instant. The technique, called ribosome profiling, led to all kinds of unexpected findings. You could see where ribosomes slowed down on a piece of mRNA, where they piled up, and where there were fewer ribosomes than expected. You could also see which mRNAs were being translated more and which ones less at different points in the life cycle of a cell. Suddenly, it became possible to ask detailed questions about what proteins the cell is making at a particular time and even in what amounts. The method has had a huge impact on understanding how ribosomes are used in the cell and where they encounter problems.