A novel stop codon readthrough mechanism produces functional Headcase protein in Drosophila trachea

Translational regulation provides an efficient means to control the localiz ation and production of proteins. The headcase (hdc) mRNA in Drosophila gen erates two overlapping proteins as a result of translational readthrough of an internal UAA stop codon. This readthrough event is necessary for the fu nction of hdc as a branching inhibitor during tracheal development. By ecto pic expression of different Hdc proteins in the trachea, we show that the l ong Hdc form alone, can function as a potent branching inhibitor whose acti vity is proportional to its amount. The suppression of termination in the h de mRNA is not stop-codon dependent, suggesting that the readthrough does n ot involve codon specific suppressors. We have identified an 80 nucleotide sequence immediately downstream of the UAA, which is necessary and sufficie nt to confer termination readthrough in a heterologous mRNA. We present a n ovel mechanism of eukaryotic translational termination suppression that may regulate the amount of functional Hdc.