New research is challenging a long-held assumption in molecular biology, and it may also help explain some confounding disorders. Publishing in Molecular Cell, scientists led by Maria Barna at Stanford University have reported that there are differences among the thousands of ribosomes in a cell. They have suggested that ribosomes are tailored to make specific proteins, rather than just acting as generic protein factories, as has long been thought.
Ribosomes take up a tremendous amount of cellular power, with cells sometimes giving over 60 percent of their energy to the construction of these organelles, which are made from RNA and 80 various types of proteins. As Jonathan Dinman, a molecular biologist at the University of Maryland in College Park explained, “Life evolved around the ribosome," which synthesize all of the proteins needed by a cell (while proteins go on to carry out the majority of cellular functions).
Although this new work is likely to be debated, "This is really an important step in redefining how we think about this central player in molecular biology," Dinman said. There have also been other reports suggesting that ribosomes are not all the same.
A mouse that was previously made by this group in 2011 that was deficient in one specific ribosomal protein had a variety of phenotypic abnormalities. The disorders of the mouse suggested that they lacked proteins crucial to development.
It has been difficult to make real progress in this field with conclusive findings, however. For this work, the scientists used a special technique to determine the levels of various proteins that comprise ribosomes. Of 15 proteins they measured, the levels of nine were equal in the assayed ribosomes, collected from mouse embryonic stem cells. However, there were four proteins not present in 30 - 40 percent of the ribosomes, showing that not all of the ribosomes were the same. Another analysis of 76 ribosomes showed specialization in seven of them.
Amazingly, the researchers went on to use a technique called ribosome profiling to determine what proteins were being made by these distinctive ribosomes. Indeed, it seemed the ribosomes did focus on groups of similar proteins. For example, one ribosome made a few proteins that control growth while another synthesized the proteins that enable cells to utilize vitamin B12. The researchers were surprised, Barna said. "I don't think any of us would have expected this."
This intriguing work could help explain some rare diseases called ribosomopathies, in which defective ribosomes cause unusual health problems. Diamond-Blackfan anemia is one example. The bone marrow that creates new blood cells is dysfunctional, and patients can also present with birth defects.
Barna suggested this may be another way for cells to modulate gene expression, although the reasons why it may be needed are not yet clear.