Unexpected functionalities of a ribosomal protein in embryonic patterning

Ribosomes are cellular machines that synthesise proteins in all cells. We have isolated a drosophila line in which one of its ribosomal proteins, RpL39, is mutated. Mutant embryos have a specific axis-patterning defect which results from reduced levels of one particular Hox protein, AbdominalA (AbdA). This suggests that AbdA requires a currently unrecognised functionality of the ribosome for efficient translation.

We will identify this functionality by dissecting the AbdA coding sequence to determine the wider subset of affected proteins. We will also test if RpL39 is acting as a component of the ribosome and identify its precise role.

This seed work seeks to understand a ribosomal protein at a fundamental level and lays the foundation to explore the wider disease context by examining conservation of RpL39 function in humans. One hypothesis is that RpL39 is critical for co-translational protein folding, which is highly relevant to human proteopathies such as Alzheimer’s and prion diseases. AbdA contains a polyglutamine tract, a feature found in several human proteins implicated in disease, and we will examine if RpL39 is critical for expression of polyglutamine tract proteins.