COMPARTMENTALIZATION OF RNA REGULATION IN THE DROSOPHILA GERM PLASM: FOUNDER GRANULE ASSEMBLY AND FUNCTION

Abstract

Posttranscriptional gene regulation plays an important role in the specification of cell fates, particularly during early embryogenesis. Formation of large ribonucleoprotein (RNP) granules serves to organize RNA molecules on the basis of their regulatory requirements. RNP granules are a prominent feature of the Drosophila germ plasm, a specialized cytoplasm at the posterior of the embryo harboring factors that are required for establishing germline fate. At least two types of granules can be distinguished. The first, which we term founder granules, contains oskar (osk) mRNA along with Staufen protein. Founder granules provide for the local production of Osk protein, which recruits additional protein and mRNA components to assemble the second type of granule, called germ granules. Germ granules are incorporated into the primordial germ cells (pole cells) as they form at the posterior of the embryo and are required for germline development. In contrast, founder granules remain largely outside of the pole cells. Aberrant targeting of osk to pole cells by packaging in germ granules impedes germline development, demonstrating the importance of segregating osk to founder granules. The work presented herein aims to characterize the assembly of osk into founder granules and to determine how this segregation prevents incorporation of excess osk in pole cells and thus protects germline development. We found that cis elements in the osk mRNA mediate the packaging of osk in founder granules, to form RNP granules that are compositionally distinct from germ granules. We show that this segregation allows for the compartmentalized degradation of osk mRNA in founder granules leading up to and during pole cell formation, thereby preventing uptake of excess osk by pole cells. Our results illustrate how segregation of mRNAs within the same subcellular location to discrete RNP granules allows for their differential regulation during subsequent stages of development.