The mitochondrial ribosomal protein mRpL4 regulates Notch signaling

Mitochondrial ribosomal proteins (MRPs) assemble as specialized ribosome to synthesize mtDNA encoded proteins which are essential for mitochondrial bioenergetic and metabolism processes. MRPs are required for fundamental cellular activities during animal development, but their roles beyond mitochondrial protein translation are poorly understood. Here we report a conserved role of the mitochondrial ribosomal protein L4 (mRpL4) for Notch signaling activation. Genetic analyses demonstrate that mRpL4 is required in the Notch signal receiving cells to permit target gene transcription during Drosophila wing development. We find that mRpL4 physically and genetically interacts with an WD40 repeat protein wap activate the transcription of Notch signaling targets. We show that human mRpL4 protein is capable of replacing fly mRpL4 during wing development. Furthermore, knock-out of mRpL4 in zebrafish leads to down-regulated expression of Notch signaling components. Thus, we have discovered a previously unknown function of mRpL4 during animal development.