A report by Yale scientists in the journal Cell sheds new light on how the protein Ro, a major autoantigen in patients with autoimmune disease, recognizes misfolded RNAs, creating a RNA quality control system for cells.
The quality control process in the cell has been well-studied for the DNA and messenger RNA (mRNA) components for making proteins. However, little was known about what cells do with abnormal or misfolded RNAs that are not translated into protein -- such as ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and small nuclear and cytoplasmic regulatory RNAs. This work describes a molecular mechanism of RNA quality control.
In the autoimmune disorders systemic lupus erythematosus and Sjogren's syndrome, Ro is known to be an autoantigen, and autoimmune disease develops in mice that lack Ro protein. This study demonstrated a connection between binding of normal RNA and "disposal" of abnormal and misfolded RNAs by Ro protein.
Collaboration between the laboratories of Assistant Professor Karin M. Reinisch and Associate Professor Sandra L. Wolin in the department of Cell Biology used both crystallography and biochemistry to visualize how Ro interacts with these RNAs.