Ribosome Profiling of 80 Human Hearts Identifies Hundreds of Small Proteins Encoded by Previously Non-Coding Regions

Systems biologist Sebastiaan van Heesch analyzed the contents of ribosomes in a collection of frozen hearts donated by 80 people in 2019. Many of the 80 heart donors had died from end-stage heart failure. Van Heesch and his team used ribosome profiling to uncover all the proteins being produced in each heart.

In addition to proteins encoded by known genes, the ribosomes were making hundreds of never-before-seen mini-proteins. The mini-proteins are molecules just a few dozen amino acids long. The code for the mini-proteins could be traced back to portions of the genome that were not thought to produce proteins.

The main destination for many of these dark proteins was the mitochondria. This raised the possibility that they were influencing the energy production process necessary for the muscles of the heart to beat properly. Stat reported the full set of findings from the ribosome profiling effort.

“All of a sudden we could look at all of these noncoding RNAs getting translated,” van Heesch said. The 2019 examination of the donated hearts produced more questions than answers for van Heesch and his team. What they found with ribosome profiling upended expectations about which parts of the genome produce proteins.

The work forms part of a broader global effort to explore the dark proteome and its possible roles in human disease.