Germ granules are ribonucleoprotein condensates that concentrate key maternal mRNAs needed for germ cell development. In Drosophila , nanos mRNA is selectively enriched in germ granules but the specific cis -acting elements mediating this process remain poorly defined. Here, we identify discrete sequence motifs in the nanos 3′ UTR that regulate nanos enrichment specifically by promoting the growth of homotypic nanos mRNA clusters within granules, without affecting the initial targeting of nanos to germ granules. These sequence motifs are binding sites for the hnRNP M homolog Rumpelstiltskin (Rump) and mutation of Rump binding sites or Rump attenuates nanos homotypic cluster growth, reducing the amount of nanos inherited by germ cells. Consequently, germ cells exhibit defective migration to the gonad. Together, our findings reveal how small repeated sequence motifs and cognate RNA-binding proteins can tune enrichment of germ granule mRNAs by driving self-assembly into large RNA clusters. This strategy ensures sufficient inheritance of mRNAs to support germ cell development and may represent a general mechanism by which RNP condensates regulate transcript dosage. • Rump-binding sites mediate nanos enrichment in, not targeting to, germ granules. • Small repeated motifs regulate nanos homotypic cluster growth. • Large clusters disproportionately contribute to total germ plasm RNA. • Rump-dependent enrichment maximizes inheritance of nanos by pole cells
Mitchel et al. (Sun,) studied this question.