Research SummaryRole of translational read through in angiogenesis regulation
Contrary to the common notion, protein translation does not always end at the stop codon. This is true even in mammals. Translating ribosomes some time continue translation beyond the stop codon to generate proteins with C-terminal extension. This phenomenon is known as translational readthrough or stop codon readthrough. The importance of translational readthrough in less complex organisms such as viruses and yeast is well established; however, its role in vertebrate biology is beginning to emerge. My postdoctoral work demonstrated that mRNA of VEGF-A, a known pro-angiogenic factor, undergoes programmed translational readthrough in mammalian endothelial cells to generate an anti-angiogenic isoform, VEGF-Ax. We have identified few more mRNAs which undergo translational readthrough in endothelial cells. Investigating these novel readthrough events is the primary goal of our laboratory.
Specifically, we are asking the following questions:
- Why does protein translation in certain mRNAs go beyond the stop codon?
- What is its biological significance?
Because of my interest in vascular biology and my previous research experience, I plan to study the importance of translational readthrough in angiogenesis executed by endothelial cells.
Figure Legend: “Genetic signal jump”: Typically stop codons (UGA, UAA and UAG) signal termination of protein translation. However, in some exceptional cases, ribosomes ‘jump’ this signal and generate longer proteins with unique properties. Our laboratory investigates these translational readthrough events in endothelial cells. Specifically, we study the molecular mechanism and the biological significance of these phenomena.