Fig. 8. Schematic representation of the proposed model on the dual role of KKE/D domains depending on growth conditions.

During exponential growth, the KKE/D domain is targeted to the close vicinity of actively transcribed rDNA genes through electrostatic interaction with nascent pre-rRNAs, without engaging in cooperative interactions with the other abundant KKE/D domains that are also associated with nascent pre-rRNAs. This specific targeting property is essential for proper activity of snoRNPs and RNA helicases in rRNA modification. In stress conditions, such as RNAPI inhibition or limited nutrient availability, during which the pre-rRNA synthesis rate declines, the proportion of latent KKE/D domain-containing AMFs increases and self-interactions among their KKE/D domains promote the cooperative concentration of these AMFs and their partners in a specific subnucleolar structure. Other early nucleolar AMFs not equipped with a KKE/D domain are excluded from these condensates. In this process, we propose that the KKE/D domains of latent snoRNPs are particularly important to increase the local concentration of GAR domain-containing proteins, allowing formation of subnucleolar condensates and subsequent sequestration of AMFs involved in the earliest stages of ribosome biogenesis (RNAPI, RNA helicases, snoRNPs).