LincRNAs enable germ cells differentiation by promoting PUF proteins condensation

Abstract

Successful tissue homeostasis depends on a balance between proliferation and differentiation. Two PUF proteins, FBF-1 and FBF-2, maintain stem-cells proliferation in C. elegans germ-cells by binding and destabilizing transcripts which promote meiotic entry. However, it is unclear how meiosis initiates because the FBF are also present at significant levels in late proliferative and early meiotic cells. We found that the three long-intergenic-non-coding RNAs (lincRNAs) that bind the FBF proteins promote timely meiotic entry. Deletion of the lincRNA genes leads to additive reduction in progenitor cell number and fertility. In the lincRNAs deletion mutant, expression of many known FBF-2 targets is significantly lower, suggesting over-activation of FBF-2. In this mutant, FBF-2 localization in perinuclear condensates is reduced, and its cytoplasmic fraction increases. Moreover, FBF-2 association with the germline P-granules decreases without the lincRNAs. Our results indicate that lincRNAs act to promote meiotic differentiation by spatially restricting pro-proliferation factors into phase-separated granules.