Unraveling the construction of cellular protein factories

2019

Challenge

Ribosomes are complex molecular machines that manufacture proteins for the cell. Consequently, they are key players in regulating gene expression, the state of physiological balance known as cellular homeostasis, and human health. Moreover, disruption of ribosome production underlies many human diseases, including cancer and neurological disorders. The assembly of ribosomes, which are comprised of one large and one small subunit, is a complex and energetically demanding process that requires the coordinated action of hundreds of compounds called ‘ribosome assembly factors’ whose functions are poorly understood.

Advance

Using a combination of genetics, biochemistry, and the Cryo-Electron Microscopy Core Facility at the NIH’s National Institute of Environmental Health Sciences (NIEHS), IRP researchers led by Stadtman Investigator Robin E. Stanley, Ph.D., determined that a protein called Rix7 plays a key role in regulating ribosome production by assisting in the formation of the larger ribosomal subunit. Rix7 performs this job by removing assembly factors from an earlier, inactive form of that ribosomal subunit.

Impact

Properly constructed ribosomes are needed to make all the body’s proteins, and these findings move researchers closer to understanding what may go wrong in diseases that occur when cells produce defective ribosomes.

Publications

YH Lo, M Sobhany, AL Hsu, BL Ford, JM Krahn, MJ Borgnia, and RE Stanley. (2019). Cryo-EM structure of the essential ribosome assembly AAA-ATPase Rix7. Nature Commun. Jan 31;10(1):513 doi: 10.1038/s41467-019-08373-0.