A DROSOPHILA RNA HELICASE GENE, PITCHOUNE, IS REQUIRED FOR CELL-GROWTH AND PROLIFERATION AND IS A POTENTIAL TARGET OF D-MYC

This article describes the characterization of a new Drosophila gene t hat we have called pitchoune (pit) (meaning small in Provence) because mutations in this gene produce larvae that cannot grow beyond the fir st instar larval stage although they can live as long as 7-10 days. Al l the tissues are equally affected and the perfectly shaped larvae are indistinguishable from first instar wild-type animals. Analysis of mu tant somatic clones suggests a function in cell growth and proliferati on, which is supported by the fact that cell proliferation is promoted by pit overexpression. Tagged-Pit, when transfected in S2 cells, loca lizes mainly to the nucleolus, pointing towards a possible role in rib osome biogenesis and, consequently, in protein biosynthesis, pit encod es a DEAD-box RNA helicase, a family of proteins involved in the contr ol of RNA structure in many cellular processes and its closest homolog ue is a human DEAD-box RNA helicase, MrDb, whose corresponding gene tr anscription is directly activated by Myc-Max heterodimers (Grandori, C ,, Mac, J,, Siebelt, F., Ayer, D. E. and Eisenman, R. N. (1996) EMBO J . 15, 4344-4357), The patterns of expression of d-myc and pit are supe rimposable. Ectopic expression of myc in the nervous system drives an ectopic expression of pit in this tissue indicating that in Drosophila as well, pit is a potential target of d-Myc, These results suggest th at myc might promote cell proliferation by activating genes that are r equired in protein biosynthesis, thus linking cell growth and cell pro liferation.