Not all of a cell’s protein-making machines do the same job

PHILADELPHIA — Protein-manufacturing factories within cells are picky about which widgets they construct, new research suggests. These ribosomes may not build all kinds of proteins, instead opting to craft only specialty products.

Some of that specialization may influence the course of embryo development, developmental biologist and geneticist Maria Barna of Stanford University School of Medicine and colleagues discovered. Barna reported the findings December 5 at the joint meeting of the American Society for Cell Biology and European Molecular Biology Organization.

Ribosomes, which are themselves made up of many proteins and RNAs, read genetic instructions copied from DNA into messenger RNAs. The ribosomes then translate those instructions into other proteins that build cells and carry out cellular functions. A typical mammalian cell may carry 10 million ribosomes. “The textbook view of ribosomes is that they are all the same,” Barna said. Even many cell biologists have paid little attention to the structures, viewing them as “backstage players in controlling the genetic code.”

But that view may soon change. Ribosomes actually come in many varieties, incorporating different proteins, Barna and colleagues found. Each variety of ribosome may be responsible for reading a subset of messenger RNAs, recent studies suggest. For instance, ribosomes containing the ribosomal protein RPS25 build all of the proteins involved in processing vitamin B12, Barna and colleagues reported July 6 in Molecular Cell. Vitamin B12 helps red blood cells and nerves work properly, among other functions. Perhaps other biological processes are also controlled, in part, by having specific types of ribosomes build particular proteins, Barna said.

In unpublished work presented at the meeting, Barna and colleagues also found that certain ribosome varieties may be important at different stages of embryonic development. The researchers coaxed embryonic stem cells growing in lab dishes to develop into many types of cells. The team then examined the ribosomal proteins found in each type of cell. Of the 80 ribosomal proteins examined, 31 changed protein levels in at least one cell type, Barna said. The finding may indicate that specialized ribosomes help set a cell’s identity.

Although Barna’s idea of diverse ribosomes goes against the classical textbook view, “the concept is not heretical at all,” says Vassie Ware, a molecular cell biologist at Lehigh University in Bethlehem, Pa., not involved in the work.

These findings may help explain why some people with mutations in certain ribosomal protein genes develop conditions such as Diamond-Blackfan anemia — a blood disorder in which the bone marrow doesn’t make enough red blood cells — but don’t have problems in other body tissues, Ware says.

That disease is caused by mutations in the RPL5 and RPL11 genes, which encode ribosomal building blocks. If all ribosomes were alike, people with mutations in ribosomal components should have malfunctions all over their bodies, or might not ever be born. RPL5 and RPL11 proteins may be part of specialized ribosomes that are important in the bone marrow but not elsewhere in the body.