19th Annual Child Health Research Days

RBC Convention Center

Oct. 24 & 26, 2023


#48 Assessing Changes in the Emg1-Utp2 Protein-Protein Interaction in the Bowen-Conradi Hutterite Syndrome Ribosomopathy

Trent Nelson, Brandon University; Courtney Harris, Brandon University; Michael Charette, Brandon University


Ribosomopathies are a new group of disorders caused by ribosome mis-assembly. They are typically associated with cancer and display an unexpected tissue proclivity. Bowen-Conradi Syndrome (BCS) is a ribosomopathy exclusively found in the Hutterites of the Canadian Prairies that presents with extreme growth retardation, skeletal deformities, and death in early childhood. It is due to a D86G mutation in the ribosome assembly/SSU processome protein Emg1. It is not clear how Emg1 is imported from the cytoplasm into the nucleolus, the site of ribosome assembly. However, the BCS mutant Emg1 accumulates in the cytoplasm and displays a nuclear import defect. Emg1’s only known protein-protein interaction (PPI) is with Utp2/Nop14, another SSU processome component. This project seeks to characterize the possibly changing PPI between wildtype (WT) or BCS Emg1 and Utp2. WT-Emg1 interacts with Utp2 and we propose that Utp2 acts as a shuttle to carry Emg1 to the nucleolus for ribosome assembly. The BCS Emg1 is believed to prefer homodimerizing with another Emg1 instead of heterodimerizing with Utp2. This altered PPI preference of the BCS mutant Emg1 is postulated to result in a nucleolar import defect for Emg1.


A yeast two-hybrid (Y2H) approach will be used to determine the PPI between WT or BCS Emg1 with Utp2. PPIs will be measured by cell growth and by β-galactosidase activity.


While WT Emg1 can interact with itself, we anticipate that it will display a PPI preference for Utp2. A reverse situation is expected with BCS Emg1, where we anticipate that it will prefer to homodimerize over interacting with Utp2.


Thus, we propose that the BCS mutation causes local misfolding of Emg1 which leads to altered PPIs as a homodimer instead of with Utp2. This may be the basis of the nuclear/nucleolar accumulation defect seen in BCS cells that leads ribosome mis-assembly.