The mitochondrial ribosomal protein mRpL4 regulates Notch signaling

Abstract

Mitochondrial ribosomal proteins (MRPs) assemble as specialized ribosome to synthesize mtDNA‐encoded proteins, which are essential for mitochondrial bioenergetic and metabolic 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) in Notch signaling. 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 the WD40 repeat protein wap and activates the transcription of Notch signaling targets. We show that human mRpL4 is capable of replacing fly mRpL4 during wing development. Furthermore, knockout of mRpL4 in zebrafish leads to downregulated expression of Notch signaling components. Thus, we have discovered a previously unknown function of mRpL4 during animal development.

Amoebicidal Effect of COVID Box Molecules against Acanthamoeba: A Study of Cell Death

“…Mitochondrial ribosomal proteins play a crucial role in the formation of the mitochondrial ribosome and are involved in the oxidative phosphorylation protein synthesis. Depletion of the mitoribosome can result in the inhibition of the oxidative phosphorylation pathways and the proper functioning of the mitochondria [ 29 ]. The DEAD box RNA helicases constitute a large family of proteins involved in various aspects of RNA metabolism including translation and ribosome biogenesis [ 30 ].…”

The Identification of RPL4 as a Hub Gene Associated with Goat Litter Size via Weighted Gene Co-Expression Network Analysis

“…Previous studies have shown that the RPL4 gene, as a protein-coding gene, plays an important role in peptide chain elongation, rRNA processing, and synthesis and is involved in functions such as RNA binding and ribosome activity. Research by Mo et al shows that RPL4 located in the mitochondria plays a unique regulatory role in mitochondrial activity and the Notch signaling pathway [42]. Deletion of RPL4 leads to decreased mitochondrial activity and interacts with the Wap-mnb complex, affecting the binding of the transcription factor Su(H) with chromatin, thus exerting significant effects on the growth and development of Drosophila and zebrafish [42].…”

“…Research by Mo et al shows that RPL4 located in the mitochondria plays a unique regulatory role in mitochondrial activity and the Notch signaling pathway [42]. Deletion of RPL4 leads to decreased mitochondrial activity and interacts with the Wap-mnb complex, affecting the binding of the transcription factor Su(H) with chromatin, thus exerting significant effects on the growth and development of Drosophila and zebrafish [42]. Research by He et al indicates that the loss of RPL4 can induce ribosomal stress, and its stable expression helps regulate the MDM2-p53 signaling loop, which is crucial for normal cell growth and proliferation [43].…”

Notch Signaling in Insect Development: A Simple Pathway with Diverse Functions

“…A disruption of Notch activity at different developmental stages could disrupt bristle pattern and bristle number, as well as cell lineage specification [ 1 , 139 ]. The aberrations in wing margin, veins and sensory bristles have become easily recognizable and reliable indicators used in genetic screens that aim to identify Notch signaling modulators [ 140 , 141 , 142 ].…”