Researchers at Burnham Institute for Medical Research (Burnham), Baylor College of Medicine (BCM) and other institutions have found that eukaryotic initiation factor 3 (eIF3), which is critical to translate genetic messages into proteins, is part of a large protein complex called the translasome, which contains the majority of the proteins needed to regulate both protein synthesis and protein degradation. The research was published in the journal Molecular Cell
on October 9.
In experiments designed to elucidate eIF3’s molecular function and perhaps target its tumor activity, Dr. Dieter Wolf, of Burnham, Dr. Eric Chang, of BCM, and colleagues at the Israel Institute of Technology in Haifa isolated the molecule from yeast cells to look at all the proteins that interact with it.
The team found that almost all the proteins needed to regulate protein synthesis and degradation form a supercomplex called the translasome. This suggests that all the components of protein synthesis need to be physically linked to work efficiently. They also found that the proteins needed to degrade proteins form a complex with those needed to make proteins.
“It’s been suspected for awhile that these processes were very close together,” said Dr. Wolf. “We were surprised to find that they are actually physically linked.”
The degradation machinery gives the cells the ability to correct many mistakes. When they can’t, they send them to the proteasome – the degradation machinery – and remove them. In fact, the translasome appears to spatially coordinate steps in the synthesis of proteins, making it more efficient. Adding the degradation machinery insures the proteins are made correctly. Those that are not are degraded and discarded.
“It’s as though the garbage can is right next to the assembly line,” said Dr. Chang.
Most of the time, the translasome exists in the cytoplasm or outer compartment of the cell, but the scientists think that it may shuttle into the nucleus, taking a type of eIF3 with it. This could have implications for the levels of translation factors found in the nucleus, although Dr. Chang notes that this remains conjecture until the proper experiments take place.
Others who took part in this research include Zhe Sha and Rodrigo Cabrera of BCM, Laurence Brill Judith S. Scheliga of Burnham and Oded Kleifeld and Michael H. Glickman of the Israel Institute of Technology in Haifa.
The full report will be available at http://www.cell.com/molecular-cell/home.